The DOI matches its Crossref record; 578 of the 585 references it cites were found in a registry or an index; none of the 274 sources its claims cite is checked for support yet.
Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell
Open accessAbstract
All soluble proteins populate conformational ensembles that together constitute the native state. Their fluctuations in water are intrinsic thermodynamic phenomena, and the distributions of the states on the energy landscape are determined by statistical thermodynamics; however, they are optimized to perform their biological functions. In this review we briefly describe advances in free energy landscape studies of protein conformational ensembles. Experimental (nuclear magnetic resonance, small-angle X-ray scattering, single-molecule spectroscopy, and cryo-electron microscopy) and computational (replica-exchange molecular dynamics, metadynamics, and Markov state models) approaches have made great progress in recent years. These address the challenging characterization of the highly flexible and heterogeneous protein ensembles. We focus on structural aspects of protein conformational distributions, from collective motions of single- and multi-domain proteins, intrinsically disordered proteins, to multiprotein complexes. Importantly, we highlight recent studies that illustrate functional adjustment of protein conformational ensembles in the crowded cellular environment. We center on the role of the ensemble in recognition of small- and macro-molecules (protein and RNA/DNA) and emphasize emerging concepts of protein dynamics in enzyme catalysis. Overall, protein ensembles link fundamental physicochemical principles and protein behavior and the cellular network and its regulation.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 274 cited sources checked · 0 supported · 0 flagged
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Cys322 is located in a well-formed helix, which is critical for catalysis.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Replica-exchange molecular dynamics simulations
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“The REMD-predicted and experimentally measured Cα SCSs show a Pearson correlation coefficient of 0.614 (Fig. 6 C), consistent with previous NMR data.371”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Replica-exchange molecular dynamics simulations
What the sources say
- Not checked yetcites [371] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Representative conformations of the top eight most-populated RMSD-based clusters (Fig. 6 A, B) reveal the both ordered and disordered nature of the K18 monomer.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Replica-exchange molecular dynamics simulations
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our REMD-generated data of K18 monomer show that cysteine-containing sequences 283DLSNVQSKCGS293 in R2 and 314DLSKVTSKCGS324 in R3 transiently sample α-helical structure (Fig. 7 A).”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Replica-exchange molecular dynamics simulations
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Conformational fluctuations of proteins in solution,11 as revealed mostly by nuclear magnetic resonance (NMR) experiments and computations, make even stable proteins exist as conformational ensembles with highly populated substates whose populations follow thermodynamic distributions.12–16”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Introduction
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Proteins with very flexible conformations, such as intrinsically disordered proteins (IDP), are expected to have larger heat capacity than well-defined proteins.96–98”
- Also stated in: § Intrinsic thermodynamic fluctuation of protein and water · hedged
“The heat capacity of IDP could be 2 to 4 times larger than globular proteins with the same molecular mass.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Intrinsic thermodynamic fluctuation of protein and water
What the sources say
Strength:plain· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § Intrinsic thermodynamic fluctuation of protein and water · hedged
In the paper
“It is the dynamic change in the distributions – via population shifts – that portrays and captures the linkage to function and life.89”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Introduction
What the sources say
- Not checked yetcites [89] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“However, the intrinsic protein energy fluctuation coupled with the local energy fluctuations in water with a range of 10 to 20 kcal/mol,93–94 is enough to perturb a well folded protein to a vast number of states.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Intrinsic thermodynamic fluctuation of protein and water
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“At thermodynamic equilibrium, structural fluctuations of proteins are not only induced by the fluctuations of intra-molecular interactions of proteins, but also by the fluctuations of the energy of the surrounding water molecules.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Intrinsic thermodynamic fluctuation of protein and water
What the sources say
- Not checked yetcites [99] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“A protein molecule in solution exists in a dynamic equilibrium mixture of sub-ensembles of conformers differing in partial molar volumes.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Intrinsic thermodynamic fluctuation of protein and water
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Changes in volume and SAS (solvent accessible surface area) are positively correlated.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Intrinsic thermodynamic fluctuation of protein and water
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“In conformations with lower volume the cavities are filled with solvent.120–121”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Intrinsic thermodynamic fluctuation of protein and water
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“In the cell, the conformational ensembles of all soluble proteins are in equilibrium around their native states.1”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Introduction
What the sources say
- Not checked yetcites [1] source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“In small proteins, domains, and disordered states, protein folding is often a two-state process132 separated by an energy barrier.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
What the sources say
- Not checked yetcites [132] source
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“The breath of the distributions of the ensembles varies across proteins; some with lower and some with higher structural variability as measured by root-mean-square deviation (RMSD) and other parameters2.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Introduction
What the sources say
- Not checked yetcites [2] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The protein compressibility βT and heat capacity Cv or Cp are directly related to the conformational fluctuations of proteins.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Intrinsic thermodynamic fluctuation of protein and water
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“more and more evidence indicates that the energy landscape dictates the conformational ensemble needed for the protein’s biological function.3”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Introduction
What the sources say
- Not checked yetcites [3] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Compared to random amino-acid sequences, the energy landscapes of natural proteins are smoother, in line with the funnel description.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The lower the volume, the more rigid the conformation would be.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Intrinsic thermodynamic fluctuation of protein and water
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“The calculated SAXS profile agrees well with the experiment.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [227] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The shallower the global energy minimum, the larger the protein fluctuation is likely to be.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Analysis of inter-subunit paramagnetic NMR data showed that free K63-Ub2 exists as a dynamic ensemble comprising multiple closed and open quaternary states.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [226] source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“This mechanism can be also illustrated by multi-scale ensemble modeling of p53 proteins with intrinsically disordered linker regions.227”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [227] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“As compared to crystal, the energy landscapes of proteins in solvent are similar to those of glass and supercooled liquid.163”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
What the sources say
- Not checked yetcites [163] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“The recognition mechanism depends on the topography of the intrinsic energy landscape.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
What the sources say
- Not checked yetcites [158] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Ligand binding sites which closely neighboring catalytic sites may enjoy moderate flexibility which accommodates ligand binding.221”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [221] source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Quaternary dynamics enables K63-Ub2 to be specifically recognized in a variety of signaling pathways.226”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [226] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As indicated in Fig. 2, intrinsically disordered proteins generally have lower energy barriers.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Therefore, on the energy landscape, the protein native state is not a single structure but a collection of conformations fluctuating at the bottom of the funnel with comparable energy and small energy barriers.160–161”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“The width and ruggedness of the unique global energy minimum determine the conformational entropy of the native state.133”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
What the sources say
- Not checked yetcites [133] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Depending on the distributions of the conformers and their conformational variability, they provide a gradient of binding site conformations of different shapes and volumes.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Hinge sites with multiple conformations are often the binding sites for multiple-ligands,219”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [219] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Even with a funnel shape, the protein folding and interaction energy landscape is necessarily rugged since a vast number of conformational states and substates exist along the folding/binding pathway as well as thermodynamic fluctuations around native state.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Consequently, the functional energy landscape has multiple minima, bridged by complex transition states.133”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
What the sources say
- Not checked yetcites [133] source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“One of the preexisting quaternary states can be selected and stabilized by a target protein.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [226] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“These can potentially favorably interact with ensembles of ligands of variable sizes.219,225”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Correlation analysis of fluorescence indicates that T4L populates multiple intermediate states.222”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [222] source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Their work confirmed that hinge regions are located near regions of high frustration, which enables allosteric proteins to exhibit rare and large-amplitude fluctuations nearly up to the opposite state basin.143”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
What the sources say
- Not checked yetcites [143] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“A combination of simulations and experiments revealed details of the conformational ensemble of the T4L.223–224”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nature has taken advantage of the ruggedness of the energy landscape to optimize proteins for their functions.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Biological signal integration through the inter-domain linkage often does not display simple additive responses to activating inputs; instead, the linker provides synergistic activation effects.217”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [217] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“The propagation of conformational change at certain locations228–230 can lead to large amplitude fluctuations of the linked domains.231”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Therefore, IDPs have also become the focus of studies of molecular mechanisms of amyloid aggregation, characterized by conformational transitions from intrinsic disorder in the soluble monomeric/oligomeric form to ordered self-assembled amyloid fibrils of the same proteins.262–263”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“The native conformational ensemble of inactive procaspase 3 is constrained by its intersubunit linker (IL).”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [236] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Here, however, as in many other cases it is a direct recognition rather than an allosteric PTM functioning through a population shift.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
What the sources say
- Not checked yetcites [256] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“However, a combination of replica exchange molecular dynamics simulations with NMR experiments showed that in the equilibrium conformational ensemble of the intrinsically disordered peptide the dominant structures present the key residues in locations thought to be critical for selective binding to β-chitin surfaces.258”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
What the sources say
- Not checked yetcites [258] source
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Combinations of PTMs can constitute an allosteric code.77”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
What the sources say
- Not checked yetcites [77] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Cleavage of the linker activates procaspase 3.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [236] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Disordered proteins provide evidence that the function of a protein and its properties are not only decided by its static folded three-dimensional structure; but by the distribution and redistribution of the conformational ensemble.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIn the paper
“The MD results also reveal similar conformational ensembles for the native and non-native ubiquitin dimers.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [232] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Disordered proteins account for a large fraction of all cellular proteins.248”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
What the sources say
- Not checked yetcites [248] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“It is noted that due to the low resolution nature of SAXS data which prevents a precise determination of relative orientation of the two monomers, the MD generated conformations differ somewhat from those fitted with the experimental structural library.232”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [232] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“They found that SAXS profiles for the two types of dimers are similar.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [232] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Interestingly, increasing the IL length by introducing 3–5 alanines can lead to constitutively active procaspases.236”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [236] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“A post-translational modification (PTM) can bias the conformational distribution, increasing the population time of a cluster favored for binding a specific partner77.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
What the sources say
- Not checked yetcites [77] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“The ensemble of L12 conformations reveals that the two C-terminal domains sample a large volume and extend further away from the ribosomal anchor than expected for a random-chain linker, indicating that the flexible linker has residual order.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [235] source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Intrinsically disordered proteins are on average twice more likely to be substrates of kinases, highlighting the importance of post-translational modifications in fine-tuning function.254”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
What the sources say
- Not checked yetcites [254] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“The sequence of the linkers and of residues in contact between linkers and adjoining domains may encode successive or parallel states through which signals travel.29”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [29] source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Stabilizing such linkers may abolish function.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“However, releasing the strain of the short IL is not enough to sufficiently increase the population of the active conformer in the native ensemble.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [236] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“The results of the analysis of the conformational ensembles of the tau proteins support the view of structured disorder and conformational selection as functional mechanism for IDPs.377”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Replica-exchange molecular dynamics simulations
What the sources say
- Not checked yetcites [377] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“These good correlations between the REMD- and NMR-derived Cα chemical shifts indicate that the REMD-generated conformational ensemble of K18 monomer is consistent with previous NMR data.371”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Replica-exchange molecular dynamics simulations
What the sources say
- Not checked yetcites [371] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“The ‘conformational selection and population shift’ model87–89,134 provides a more realistic description of the molecular mechanism considering the ensemble nature of protein molecules.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control
What the sources say
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“The close lysine-cysteine contacts in K18 may facilitate tau’s self-acetylation activity mediated by cysteine residues as reported recently.379”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Replica-exchange molecular dynamics simulations
What the sources say
- Not checked yetcites [379] source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Tau proteins possess intrinsic enzymatic activity capable of catalyzing self-acetylation mediated by a pair of catalytic cysteine residues residing within the microtubulin (MT)-binding domain.373”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Replica-exchange molecular dynamics simulations
What the sources say
- Not checked yetcites [373] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“MSMs can predict kinetic quantities on long timescales (e.g. milliseconds) using a set of much shorter MD simulations.395–396”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Markov state models
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Symmetrical oligomeric complexes are evolutionarily selected by functional, genetic, and physicochemical needs.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-protein complexes
What the sources say
- Not checked yetcites [266] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“A Markov state model (MSM), known as a stochastic model, provides an approach which can be used to identify the kinetically relevant states and the rates of interconversion between these states.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Markov state models
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“These methods alone, or in combination with high-resolution experimental techniques such as x-ray crystallography and NMR, have been successfully applied to the study of the free energy landscape of flexible proteins and protein oligomers,36,388–389 peptide folding,390–392 ligand and selective ion permeation through cell membrane protein channels.393”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Metadynamics simulations
What the sources say
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“These two regions are highly similar to the catalytic regions in MYST-family acetyltransferase Esa1 and Tip60.379”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Replica-exchange molecular dynamics simulations
What the sources say
- Not checked yetcites [379] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Protein-protein interfaces are characterized by the existence of hot spots or ‘hot regions’ in interacting regions instead of an even contribution across all contact areas.371,476,487,492–495”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“The structural ensemble in DHFR is exquisitely optimized for every intermediate in the catalytic cycle.461”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
What the sources say
- Not checked yetcites [461] source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is easy to understand that conformational ensemble heterogeneity promotes enzyme promiscuity.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Conformational ensembles enable enzymes to function through multiple steps.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Using experimentally known protein conformational ensembles in modeling protein-protein interactions on the proteome scale can boost the percentage of successfully predicted interactions from ~26 to 66%.478”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [478] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“They found that in more than 70% of the examined enzymes, the global hinge centers predicted by the GNM are colocalized with the experimentally identified catalytic sites.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
What the sources say
- Not checked yetcites [221] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“The rate by which the enzyme converts substrates into products is not the speed of the chemical step.448”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
What the sources say
- Not checked yetcites [448] source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Protein-protein interactions and other cellular networks have the ability to adjust their internal states to incoming stimuli.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“MD simulations and free energy calculations revealed the crucial role of protein flexibility in formation of a stable reaction transition state in α-amylase catalysis.451”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
What the sources say
- Not checked yetcites [451] source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Enzymes are optimized by evolution to exploit conformational ensembles to recognize their substrates and stabilize the transition states,70,209 and both experimental and theoretical evidence indicates that enzyme conformational transitions are highly organized which increases enzyme specificity and efficiency.133,399,433–435”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Overall, ensemble receptor-based protocols display a stronger discriminating power between active and inactive molecules as compared to its standard single rigid receptor counterpart.426”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-small molecules interactions
What the sources say
- Not checked yetcites [426] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“It has been shown that SOS functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average.472”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
What the sources say
- Not checked yetcites [472] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“During binding, higher energy (lower population) conformers which are most complementary to some pre-existing ligand conformations can be selected and the equilibrium shifts toward these conformers.87–89,134”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“In this case, the ability of MUP-I to bind different lipophilic ligands derives from a limited extent of conformational flexibility and unoccupied space within the hydrophobic interior of the β-barrel.413”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-small molecules interactions
What the sources say
- Not checked yetcites [413] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As compared to globular proteins with flexible binding sites, the interactions of intrinsically disordered proteins with small molecules are much harder to track either experimentally or computationally.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-small molecules interactions
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear? Based: unclearIn the paper
“Targeting the intrinsically disordered structural ensemble of α-synuclein by small molecules as a potential therapeutic strategy for Parkinson’s disease has been shown to be promising.429”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-small molecules interactions
What the sources say
- Not checked yetcites [429] source
Strength:boosted· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Protein dynamics have been shown to be universally important for protein-ligand interaction.219”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-small molecules interactions
What the sources say
- Not checked yetcites [219] source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Conformational sampling for bacterial phosphotriesterase,443 maltose binding protein,444 and choline oxidase,445 cytochrome bc1 complex,446 and many other lid-gated enzymes indicated that the closed and open conformations are in equilibrium prior to ligand binding, permitting a conformational selection pathway at different catalytic steps.447”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Enzyme specificity can be controlled through multiple conformational selection steps.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ensemble-averaged states sometime are not applicable to enzymes with distinct functional states.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Different protein conformations often correspond to different biological functions.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-small molecules interactions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The catalytic power of enzymes largely derives from their ability to stabilize transition states, lowering the barrier that reactants have to pass to reach productive states.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Recently, it has been found that ATP turnover by individual myosin molecules uses two conformers of the myosin active site, one that allows the complete ATPase cycle and one that dissociates ATP uncleaved.467”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
What the sources say
- Not checked yetcites [467] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Serine protease is conventionally regarded as fitting the rigid lock-and-key model. However, nanosecond timescale binding loop movement was observed to select an inhibitor conformation.465”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
What the sources say
- Not checked yetcites [465] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“whereas the residues surrounding the conserved residues may form a flexible cushion.496”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [496] source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Antibody evolution may constrain conformational heterogeneity by tailoring protein dynamics.519”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [519] source
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Coupling of rigid hot spot and flexible protein regions can be an efficient way to adjust protein-protein interaction energy.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Controlled evolution of the antifluorescein antibody 4–4-20 localized the Ab-combining site from a heterogeneous ensemble of conformations to a single conformation by introducing mutations that act cooperatively and over significant distances to rigidify the protein.519”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [519] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Antibody evolution and conformational changes are similar to point mutations within the ubiquitin core, which changes the binding specificity allosterically by shifting the conformational equilibrium of the ground-state ensemble between open and closed substates that have similar populations in the wild-type protein.521”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [521] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“It was also found that correlated flexibility may increase during antibody complex formation.520”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [520] source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“The results indicated that the specificity is not only controlled by the final stage of the interaction across the protein-protein interface, but also contributed by dynamic intermediate stages along the pathway from the separated Eph and ephrin to the Eph-ephrin complex.514”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [514] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“In comparing two scFv mutants with similar thermodynamic stability, local and long-ranged changes in backbone flexibility are observed.520”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [520] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Antibody-antigen interactions optimize the coupling of rigid and flexible protein binding sites for specific antigen binding.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: Antibody variable regions must be flexible to recognize highly diversified targets.
In the paper
“The ensembles were optimized through shape clustering, revealing distinct subclass-specific conformational preferences.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [517] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“This mechanism appears to be in addition to other mechanisms adopted by hub proteins, such as covalent linkage to protein interaction domains, alternative splicing variants, etc.524”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [524] source
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In cases of multiple-partner binding, or in altered homo-multimeric organization, the different binding modes are accomplished through distinct conformers from the ensemble, explaining the so-called ‘promiscuous’ binding.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Bioinformatics analysis indicated that human centrosomal proteins have a significant bias to be both unstructured and with coiled-coil regions with respect to generic human proteins.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [526] source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“The specific differences in the linker region correlate with the solution structure of intact antibodies.517”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [517] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Conformational dynamics and the distribution of the conformational ensemble are important in Eph-Ephrin recognition.9,475,513–516”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Depending on the function of the complex, protein-protein interactions may have a broad range of binding energies.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The wide distribution of the conformational ensemble of flexible protein enables hub proteins to bind a large number of partners with different binding modes.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Several hot spots in the Eph binding pocket were identified as important for the binding of several peptides.475”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [475] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Evidence of conformational selection driving the formation of ligand binding sites in protein-protein interfaces has been shown in one study which focused on ensembles of ligand-free protein conformations obtained by NMR.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [502] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“but the large interfaces area does not necessarily equate to high affinities.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The change and optimization of the conformational ensemble also allow allosteric antibody interaction.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Highly fluctuating conformations of intrinsically disordered proteins offer functional advantages in protein-protein interactions.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Natively disordered proteins can form ordered complexes upon binding their partner.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eph-Ephrin recognition is a good example for the coupling of rigid and flexible protein binding sites to adjust ‘promiscuous’ and specific protein-protein interactions.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Hot spot residues at binding interfaces confer rigidity to minimize the entropic cost of binding”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [496] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Clearly, nature utilized conformational selection to fit specific targets.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“They found that the ensemble model generated reliable responses that match experimental observations.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensembles and molecular machines
What the sources say
- Not checked yetcites [535] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“KIX is an allosteric domain able to bind two other proteins cooperatively.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [530] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Different partners binding at the second site can modulate the conformations and thus the affinity of pKID-KIX interaction, regulating the transactivation complex.530”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [530] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“In the classic example of muscle contraction as biomolecular machines, the release of chemical energy is often accompanied by thermal fluctuation, which can transform muscular force generated in response to external stimuli through cyclical interactions between myosin and actin.539”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensembles and molecular machines
What the sources say
- Not checked yetcites [539] source
Strength:plain· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“The complexity of gene regulation requires a combination of high and low affinity DNA binding.543”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-RNA/DNA interactions
What the sources say
- Not checked yetcites [543] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“The results illustrated on the cellular systems level that ensembles are able to signal effectively through a multiple-conformations combinatorial scheme that represents a form of weak linkage.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensembles and molecular machines
What the sources say
- Not checked yetcites [535] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“In contrast, the model that employs hierarchical assembly pathways to produce scaffold-based signaling machines could not replicate experimental observations.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensembles and molecular machines
What the sources say
- Not checked yetcites [535] source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“RNA and DNA also exist as conformational ensembles, no matter whether in freely diffusing state,540 in crystal,541 or in large nucleosomes,542 ribosomes, or spliceosomes.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-RNA/DNA interactions
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ensembles conceptualize parallel signaling pathways whose abundance reflect concentrations of cofactors and second messengers and cell states, including interplay with post-translational”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensembles and molecular machines
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Conformational ensembles are essential for molecular machine tasks requiring high specificity.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensembles and molecular machines
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Since signaling and other regulatory complexes typically consist of highly dynamic molecular ensembles a ‘conventional’ mechanical description of protein complexes that requires well-defined quaternary structures is misleading.534–535”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensembles and molecular machines
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Thermodynamically, both enzymes and molecular motors can be described by ensembles of a discrete set of states.532–533”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensembles and molecular machines
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 61
- Probably not a substantial claim. 8
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In a typical case, the partial molar volume change is about −20 to −100 mL/mol, which means the free energy change is on the order of −0.5 to −2 kcal/mol per 1 kbar which may be sufficient to shift state B as the dominant species under elevated pressure in place of state A.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Intrinsic thermodynamic fluctuation of protein and water
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“One could estimate that the root mean square fluctuations of E and V are respectively:16 〈ΔE2〉≈38kcalmol−1, 〈ΔV2〉≈80Å3.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Intrinsic thermodynamic fluctuation of protein and water
What the sources say
- Not checked yetcites [16] source
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The lysine−cysteine distance distribution curve in Fig. 7 (B) displays peaks between 5 and 10 Å, indicating that the two residues are close enough as in acetyltransferase with a Cα−Cα distance of 8.4 Å between Lys262 and Cys304.380”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Replica-exchange molecular dynamics simulations
What the sources say
- Not checked yetcites [380] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mapping the folding landscape to a single coordinate, such as the fraction of native contacts, the energy landscape can be visualized as a funnel,132 elegantly resolving Levinthal’s paradox.11”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“The more flexible are the proteins the larger the number of their populated states, with the disordered state being at the end of this spectrum.17”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Introduction
What the sources say
- Not checked yetcites [17] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The statistical energy landscape theory was developed to study protein folding.1,128–131”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“It is now generally accepted that crystal proteins may still have different conformations in a single unit cell,9 and there are multiple, populated substates that are not captured in the crystal state.10”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Introduction
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“There are two mechanisms for a protein in solution to attain a lower volume in response to pressure: ‘elastic response’ by general compression within the sub-ensemble of the conformers and a shift of the conformational equilibrium from a high-volume to a low-volume ensemble.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Intrinsic thermodynamic fluctuation of protein and water
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Protein structures must be considered as dynamic objects at the molecular level due to their intrinsic thermodynamic fluctuations16,92 as well as those of water.93–94”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Intrinsic thermodynamic fluctuation of protein and water
What the sources say
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here our thesis is that the distributions of the states on the energy landscape are determined by statistical thermodynamics; however, they are also modulated by function which is optimized by evolution.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Introduction
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
- The authors state this as an assumption: Protein function has been optimized by evolution.
None of the sources cited for this claim have been checked yet.
In the paper
“The pivotal concept that all conformations pre-exist and are sampled by thermodynamic fluctuations – with function involving not new conformations but a shift in their relative concentration – underlies current approaches and interpretations.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Introduction
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The minimum frustration principle implies that nature has optimized protein folding,129,174 thus the effect of point mutations on the energy landscape is analogous to thermal perturbations.175”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“For example, the energy landscape roughness slows down dissociation kinetics and can contribute to streptavidin-biotin interaction dynamic strength.176”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
What the sources say
- Not checked yetcites [176] source
Strength:plain· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The energy landscape concept was extended to protein-ligand binding and function87–89,134–141 and statistical approaches were developed to describe the protein binding energy landscape.142–158”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
What the sources say
- Not checked yetcites [87] source
- Not checked yetcites [88] source
- Not checked yetcites [89] source
- Not checked yetcites [134] source
- Not checked yetcites [135] source
- Not checked yetcites [136] source
- Not checked yetcites [137] source
- Not checked yetcites [138] source
- Not checked yetcites [139] source
- Not checked yetcites [140] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Exploiting the concept of glasses and supercooled liquids,166 protein motions could be classified by the α fluctuation (primary) and βh fluctuation (secondary).167–168 The slower α relaxation motions are inversely controlled by the solvent viscosity169–170 and the faster βh fluctuations are largely due to the hydration shell of the proteins.171”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
What the sources say
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“However, long-range contacts in the p53 linker region were required to reproduce the experimental SAXS profile, indicating allosteric communication.227”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [227] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“mutations at the hinge regions could allosterically affect the binding-site dynamics or induce alternative binding modes by modifying the ensemble of accessible conformations220.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [220] source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The local glass transition temperature TG is proportional to the fluctuation energy, and therefore the protein folding frustration TF/TG is inversely proportional to the fluctuation energy.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Thermodynamic principle of protein molecules > Thermodynamic fluctuations and the energy landscape theory
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“The results indicated that the linker sequence is not randomly distributed; the resulting conformational ensemble of the linker must be optimized for calmodulin binding.234”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [234] source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“In the case of p53, phosphorylation at Ser20 turns off p53-MDM2 binding, with a consequent increase in p53 concentration; while phosphorylation at Thr155 targets p53 to degradation by the ubiquitin system (reviewed in256).”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
What the sources say
- Not checked yetcites [256] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“‘Disordered’ or ‘intrinsically unstructured’ proteins lack a stable, well-defined structure under physiological conditions, existing in a continuum of conformations from the less to the more structured states.240–243”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
What the sources say
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Many proteins either contain at least one intrinsically disordered region (IDR) (such as intrinsically disordered domains and linkers in multidomain proteins)234,237 or are completely disordered (such as IDPs which are highly flexible and dynamic).238–239”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The active state of a specific function is a unique state, which is not the case for the inactive states; its stability (population) may increase through a shift of the ensemble, e.g. via binding.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: For a given protein function, the active state is unique while inactive states are not unique.
In the paper
“The conformational ensemble of PaaA2 is highly compact and in solution the protein exists as two preformed helices, connected by a flexible linker where the helices may act as molecular recognition elements for toxin inhibition.259”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
What the sources say
- Not checked yetcites [259] source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“They identified 10 residues in the interdomain linker region that change their conformations upon substrate binding, including five flexible residues (Met76, Lys77, Thr79, Asp80 and Ser81) and five rigid residues (Arg74, Lys75, Asp78, Glu82 and Glu83).”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [234] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“One such example is the p53 protein, which has more than a dozen phosphorylation and acetylation sites with different biological signals.256”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
What the sources say
- Not checked yetcites [256] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The structures of disordered proteins are not ‘random’. Rather, the disordered state has significant metastable structures.240–243,257”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
What the sources say
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Even though they appear to challenge the paradigm of structural biology, that function requires distinct 3D structure, this is not the case, since function involves a specific selected state, which may have marginal stability and low barriers, thus short residence time which may evade detection.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
- Rests on an assumption: For a given protein function, the active state is unique while inactive states are not unique.
In the paper
“The regulation of unstructured proteins in the cell can occur at multiple levels of mRNA transcription and degradation; protein translation and degradation; and fidelity control of transcription and translation, including post-translational modifications in functional/degradation control.254”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
What the sources say
- Not checked yetcites [254] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“The combination of optimal length, IL flexibility, and specific contacts between the IL and interface are needed to stabilize the active state.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [236] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“It was suggested that anti-correlation of the distances between each C-terminal domain and the anchor promotes the function of L12 to recruit translation factors and control their activity on the ribosome.235”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-domain proteins with hinge motions or linkers
What the sources say
- Not checked yetcites [235] source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Intrinsically disordered linkers connecting folded domains and intrinsically disordered domains usually encode the degrees of conformational flexibility essential for protein function,17,29,244–250,239,247,249–253 including regulation of transcription and translation, cellular signaling, phosphorylation, regulation of large multi-molecular self-assemblies and small molecule storage.249”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Disordered proteins
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The ‘induced fit’ hypothesis412 suggests that the bound conformation can be ‘induced’ by the binding partner when the conformation in the complexes differs from that in the unbound form.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control
What the sources say
- Not checked yetcites [412] source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“demonstrated that the conformational ensembles of histone tails are composed of states with various degrees of residual order and most tails are not fully disordered, but show distinct conformational organization, containing α-helical elements and β-hairpins.368”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Replica-exchange molecular dynamics simulations
What the sources say
- Not checked yetcites [368] source
Strength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, these studies revealed the potential of MSMs to identify putative allosteric binding sites or to differentiate between agonists and antagonists using conformational information along putative functional pathways.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Markov state models
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Oligomeric proteins with two or more subunits comprise about one third of the cellular proteins,266–267 most of them symmetrical.266”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Structural (and sequence) modules in protein conformational ensembles > Multi-protein complexes
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“IDPs adopt multiple conformations for function;377–378 that is, the multiple conformational ensembles collectively determine functions.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Replica-exchange molecular dynamics simulations
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Markov state models have been applied to a wide variety of problems, spanning protein folding,402 protein-ligand binding process,403 protein conformational change,404–405 the dynamics and kinetics of IDPs,369,406–407 and ATP permeation through membrane protein channels.408”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Markov state models
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Proteins and their binding partners are flexible and exist in ensembles with certain conformational distributions.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control
What the sources say
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Similar to the REMD method, metadynamics is also an enhanced sampling method which is widely used to explore the conformational space of biomolecules.314,381”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Metadynamics simulations
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Enhanced sampling methods such as REMD and metadynamics can provide the structural and thermodynamic properties of proteins. However, they do not reproduce kinetic rates and conformational dynamics.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Markov state models
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Acetylation of tau inhibits its function and promotes pathological aggregation.373–375”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Experimental and computational methods to characterize protein ensembles > Replica-exchange molecular dynamics simulations
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Molecular dynamics simulations of CypA show that the ensembles of enzyme conformations recognize diverse inhibitors and bind different configurations of the peptide substrate.3”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
What the sources say
- Not checked yetcites [3] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“GPCRs exhibit multiple inactive and active conformations, and the population balance between these conformations is altered upon binding of ligands.415”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-small molecules interactions
What the sources say
- Not checked yetcites [415] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The protein conformational ensemble not only allows enzymes to catalyze multiple chemical steps, but accommodates the conformational reorganization required to stabilize the transition states.449”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
What the sources say
- Not checked yetcites [449] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The docking algorithm was validated on 10 protein ensembles containing 105 crystal structures and 87 ligands and achieved a success rate of 93%, significantly better than single rigid-receptor docking (75% on average).425”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-small molecules interactions
What the sources say
- Not checked yetcites [425] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Therefore, receptor activation depends on both low energy states and the range of the conformations sampled by the receptor.416”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-small molecules interactions
What the sources say
- Not checked yetcites [416] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“An earlier QM/MM study468 demonstrated that R55K substitution at the active site of CypA leads to a significant decrease in catalysis, indicating that the active site stability likely plays an important role in the chemical step of catalysis.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
What the sources say
- Not checked yetcites [468] source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“It has been shown that ligands can interact with similar targets in different conformations, and that the biological outcomes like ERβ selective agonist depend on the relative affinities of a ligand to ensembles of protein conformations.414”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-small molecules interactions
What the sources say
- Not checked yetcites [414] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Comparison of the apo and holo equilibrium ensembles reveals that c-Myc binding conformations are already partially formed in the apo ensemble, suggesting a conformational selection mechanism.432”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-small molecules interactions
What the sources say
- Not checked yetcites [432] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“This correlation could suggest that protein motions necessary for catalysis are an intrinsic property of the enzyme and might even limit the overall turnover rate.469”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
What the sources say
- Not checked yetcites [469] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The conformational ensemble and population shift allow the enzyme to bind the co-substrate prior to the substrate, and can also limit premature release of substrate.442”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensemble in enzyme catalysis
What the sources say
- Not checked yetcites [442] source
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The disordered state has a significant metastable structure character240–243,257 and functionally relevant conformations may have population times higher than of other conformations.240–242”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-small molecules interactions
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“They found that promiscuous residues tend to be more flexible, and this additional flexibility permits a broader range of organizations which could take place in different conformers in the ensemble.523”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [523] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Obviously, the most flexible proteins are the disordered proteins, with some more folded than others.525”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [525] source
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“This bias implies that they adopt an ensemble of disordered and partially helical conformations, with the latter becoming stabilized when these proteins form complexes, depending on pH and concentration.527”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [527] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Often, weak complexes have smaller contact area and the interfaces are more planar and with more polar residues,511”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [511] source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Even though antibody-antigen interfaces have fewer hot spot residues,496,518 Tyr is a preferred hot spot residue for immunoglobulins.119a”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Dynamic conformational changes during the Eph-ephrin recognition were found to be stepwise conformational selection and population shift events, with two dynamic salt bridges between EphB4 and Ephrin-B2 contributing to specific recognition.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [514] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Some associations are obligatory where one protein is bound to another throughout its functional lifetime, whereas others are transient, continuously forming and dissociating503–510.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“For example, the interactions of nidogen-1 with laminin variants indicate the existence of a conformational ensemble of both individual proteins and complex, implying different modes of interaction through distinct protein-protein interfaces.522”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [522] source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Centrosomal proteins tend to be larger than a control set of human proteins, and are rich in predicted disordered regions, which cover 57% of their length, compared to 39% in the general human proteome.526”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [526] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“the binding affinities of EphA4 with ephrin-A1, ephrin-A2, ephrin-A4, ephrin-A5, and ephrin-B2 are 1.2 μm, 2.3 μm, 36 nm, 360 nm, and 10.8 μm, respectively,512 indicating varied selectivity towards various ligands.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [512] source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Such a cellular strategy facilitates variable response to the environment and gain of function in network evolution.535”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein ensembles and molecular machines
What the sources say
- Not checked yetcites [535] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Interestingly, protein disorder in the centrosome correlates with complexity with the number of cell types, and the structural heterogeneity conferred by the disordered regions and phosphorylation playing an important role in its mechanical properties and regulation in space and time.528”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [528] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Since RNA and DNA carry generic information, protein-RNA/DNA interactions should ensure correct processing of genomic information.”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-RNA/DNA interactions
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
- Rests on an assumption: Protein-protein and protein-RNA/DNA interactions follow the same physico-chemical principles.
- Rests on an assumption: RNA and DNA are dynamic molecules.
In the paper
“When unphosphorylated and unbound, KID is disordered. Cooperative folding and binding occur upon pKID–KIX interaction, forming two α-helices kinked near the phosphorylated site.529”
§ Protein ensembles: how does nature harness thermodynamic fluctuations for life? > Protein interactions and reactions under ensemble control > Protein-protein recognition
What the sources say
- Not checked yetcites [529] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The authors state this as an assumption.
Protein function has been optimized by evolution.
“modulated by function which is optimized by evolution”
The paper relies on this without support.
For a given protein function, the active state is unique while inactive states are not unique.
“The active state of a specific function is a unique state, which is not the case for the inactive states;”
The paper relies on this without support.
Conformational states and dynamics observed in isolated, reconstituted, or computational systems correspond to functionally relevant states in the living cell.
“In the heterogeneous cellular environment, protein conformations including those of symmetric oligomers may differ across time and space.”
The paper relies on this without support.
Macromolecular crowding in cells can be represented by the experimental and simulation crowding models discussed.
“In the cellular environment, the high concentration of macromolecules creates crowding effects.”
The paper relies on this without support.
Antibody variable regions must be flexible to recognize highly diversified targets.
“Antibody variable regions are necessarily flexible to enable recognition of tremendously diversified targets.”
The paper relies on this without support.
Natively disordered proteins can form ordered complexes upon binding their partner.
“Upon binding their partner, natively disordered proteins can form ordered complexes.”
The paper relies on this without support.
Cell-signaling proteins have disproportionately intrinsically unstructured regions.
“Cell-signaling proteins also have disproportionately intrinsically unstructured regions.”
The paper relies on this without support.
Protein-protein and protein-RNA/DNA interactions follow the same physico-chemical principles.
“Protein-protein and protein-RNA/DNA interactions should follow the same physico-chemical principles.”
The paper relies on this without support.
RNA and DNA are dynamic molecules.
“Both RNA and DNA are dynamic molecules.”
The paper relies on this without support.
Protein conformational ensembles correlate with gene regulation.
“Protein conformational ensembles should correlate with gene regulation.”
The paper relies on this without support.
Biomacromolecules are dynamical objects that continuously interconvert between structures of varying energies.
“Biomacromolecules are dynamical objects; they continuously interconvert between structures with varying energies.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Native conformations of proteins are often described as time averaged ensembles of conformations with Boltzmann-type distributions, especially IDPs and proteins with IDRs100,101.”
From The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins (2024) · cites this paper as [101]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Temperature and volume are interchanged in the variable definitions
MinorThe list assigns T to volume and V to temperature, but the paper explicitly defines V as volume earlier in the same section.
“Here Cv and Cp are the heat capacity of the system at constant volume and at constant pressure, and kB, m, T, V and βT is Boltzman constant, mass, volume, temperature, and isothermal compressibility of the system, respectively.”
“X2i=volume (V)”
Citations
Cites
Laio, A., & Parrinello, M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.202427399 · Cited by 5,626
Protein folding and misfolding
Dobson, C. M. (2003) · Nature · doi:10.1038/nature02261 · Cited by 4,791
Replica-exchange molecular dynamics method for protein folding
Sugita, Y., & Okamoto, Y. (1999) · Chemical Physics Letters · doi:10.1016/s0009-2614(99)01123-9 · Cited by 4,499
Intrinsically unstructured proteins and their functions
Dyson, H. J., & Wright, P. E. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1589 · Cited by 3,871
Stochastic thermodynamics, fluctuation theorems and molecular machines
Seifert, U. (2012) · Reports on Progress in Physics · doi:10.1088/0034-4885/75/12/126001 · Cited by 3,300
The Energy Landscapes and Motions of Proteins
Frauenfelder, H., Sligar, S. G., & Wolynes, P. G. (1991) · Science · doi:10.1126/science.1749933 · Cited by 3,250
Well-Tempered Metadynamics: A Smoothly Converging and Tunable Free-Energy Method
Barducci, A., Bussi, G., & Parrinello, M. (2008) · Physical Review Letters · doi:10.1103/physrevlett.100.020603 · Cited by 3,184
Funnels, pathways, and the energy landscape of protein folding: A synthesis
Bryngelson, J. D., Onuchic, J. N., Socci, N. D., & Wolynes, P. G. (1995) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.340210302 · Cited by 2,648
Dynamic personalities of proteins
Henzler-Wildman, K., & Kern, D. (2007) · Nature · doi:10.1038/nature06522 · Cited by 2,545
The amyloid state and its association with protein misfolding diseases.
Knowles, T. P. J., Vendruscolo, M., & Dobson, C. M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3810 · Cited by 2,382
Flagged first, then by citations
7 of the 585 references couldn’t be matched to a known paper.
Research works printed but not linked: 14
- 10.1063/1.455536 · DOI · Paper page
- Gekko K., 2015, High Pressure Bioscience, 72, 10.1007/978-94-017-9918-8_5 · DOI
- Dickson A., 2015, J. Comput. Chem.
- 10.1073/pnas.92.8.3626 · DOI · Paper page
- 10.1096/fj.14-257287 · DOI
- 10.1186/2046-1682-5-2 · DOI · Paper page
- 10.1021/jz501457f · DOI
- 10.1002/prot.1107 · DOI · Paper page
- 10.1111/j.1742-4658.2005.04948.x · DOI · Paper page
- 10.1038/nsmb.2555 · DOI · Paper page
- Menichetti G., 2014, Theor. Biol. Forum., 107, 77
- Laskowski R. A., 1996, Protein Sci., 5, 2438
- 10.1002/prot.1107 · DOI · Paper page
- 10.1016/s0968-0004(03)00003-3 · DOI
Cited by
Sorted by citations
Lipinski, C. A. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.04.029 · Cited by 626
The roles of structural dynamics in the cellular functions of RNAs
Ganser, L. R., Kelly, M. L., Herschlag, D., & Al‐Hashimi, H. M. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0136-0 · Cited by 563
Sun, Z., Liu, Q., Qu, G., Feng, Y. F., & Reetz, M. T. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00290 · Cited by 529
Babu, M. M. (2016) · Biochemical Society Transactions · doi:10.1042/bst20160172 · Cited by 431
Nonspecific Binding—Fundamental Concepts and Consequences for Biosensing Applications
Frutiger, A., Tanno, A., Hwu, S., Tiefenauer, R. F., Vörös, J., & Nakatsuka, N. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00044 · Cited by 287
Metadata
- Authors
- Wei, G., Xi, W., Nussinov, R., & Ma, B.
- Affiliations
- Fudan University (CN)
- Tel Aviv University (IL)
- National Cancer Institute (US)
- Corresponding author
- Wei, Guanghong
- Ma, Buyong
- Venue
- Chemical Reviews
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-01-25
- Volume
- 116
- Issue
- 11
- Pages
- 6516-6551
- ISSN
- 0009-2665 (ISSN-L)
- 1520-6890
- PMC
- PMC6407618
- OpenAlex
- W2265800909
- Semantic Scholar
- deccc9316ec26c52d5390bfa2f621c6e68cebe6c
- Cited by
- 436
- References
- 585
- Citations by year
- 2026: 57 · 2025: 48 · 2024: 34 · 2023: 42 · 2022: 43 · 2021: 42 · 2020: 36 · 2019: 45 · 2018: 33 · 2017: 35 · 2016: 20
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Chemical Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (HHSN261200800001E)
- National Natural Science Foundation of China (11274075, 91227102)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- protein conformational ensembles, free energy landscape, thermal fluctuations, protein flexibility, intrinsically disordered proteins, multidomain proteins, protein complexes, intracellular crowding, protein-ligand recognition, enzyme catalysis, protein dynamics, replica exchange molecular dynamics, metadynamics, Markov state models
- MeSH terms
- Humans, Markov Chains, Protein Conformation, Proteins, Thermodynamics, Nuclear Magnetic Resonance, Biomolecular, Molecular Dynamics Simulation, Protein Interaction Maps, Intrinsically Disordered Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
