AlphaFold and Implications for Intrinsically Disordered Proteins
Open accessAbstract
Accurate predictions of the three-dimensional structures of proteins from their amino acid sequences have come of age. AlphaFold, a deep learning-based approach to protein structure prediction, shows remarkable success in independent assessments of prediction accuracy. A significant epoch in structural bioinformatics was the structural annotation of over 98% of protein sequences in the human proteome. Interestingly, many predictions feature regions of very low confidence, and these regions largely overlap with intrinsically disordered regions (IDRs). That over 30% of regions within the proteome are disordered is congruent with estimates that have been made over the past two decades, as intense efforts have been undertaken to generalize the structure-function paradigm to include the importance of conformational heterogeneity and dynamics. With structural annotations from AlphaFold in hand, there is the temptation to draw inferences regarding the "structures" of IDRs and their interactomes. Here, we offer a cautionary note regarding the misinterpretations that might ensue and highlight efforts that provide concrete understanding of sequence-ensemble-function relationships of IDRs. This perspective is intended to emphasize the importance of IDRs in sequence-function relationships (SERs) and to highlight how one might go about extracting quantitative SERs to make sense of how IDRs function.
AI snapshot
Written from the paper’s full text.
TL;DR
This perspective cautions against over-interpreting AlphaFold’s low-confidence and “unstructured” annotations for intrinsically disordered regions as literal structures or as failures of prediction. It argues that quantitative sequence–ensemble descriptions, not static models, are needed to understand IDR function.
Key findings
- AlphaFold annotated over 98% of human proteome sequences, but roughly 30% of residues have pLDDT scores below 50, consistent with estimates that about 30% of the human proteome is disordered.
- Low-confidence regions largely overlap intrinsically disordered regions (IDRs); the authors argue most are likely genuinely disordered rather than well-folded structures that AlphaFold missed.
- Static AlphaFold structures of IDRs often overestimate radius of gyration relative to SAXS measurements, as shown for p27 CTD and the hnRNP-A1 prion-like low-complexity domain (A1-LCD).
- Quantitative ensembles from atomistic simulations vetted by experiments reveal sequence-specific behavior: p27 CTD behaves on average like a Flory random coil, A1-LCD uses aromatic stickers/spacers, and Httex1 prefers tadpole-like conformations with polyQ radius scaling as n^1/3.
Methods
- Perspective/cautionary note, not primary research; it synthesizes the AlphaFold papers, human proteome annotations, and prior IDP literature.
- Uses illustrative examples—p27 Kip1 CTD, hnRNP-A1 A1-LCD, and huntingtin exon 1 (Httex1)—comparing AlphaFold static structures with SAXS, NMR, smFRET, and atomistic simulations based on the ABSINTH implicit solvation model and forcefield.
- Main analysis is interpretive and qualitative, focused on why static AlphaFold depictions of IDRs lack physical meaning and how sequence–ensemble relationships should instead be quantified.
Limitations
- The paper does not state formal limitations.
- Evident from the text: it is a perspective/opinion piece, not a systematic review, and its examples are drawn largely from the authors’ own work and close colleagues.
- Evident from the text: no new experimental data are reported; the quantitative examples rely on previously published simulations and experiments, and the scope is limited to interpreting AlphaFold annotations for IDRs.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 58 cited sources checked · 0 supported · 0 flagged
- Findingcitation
Integrating SAXS and NMR measurements with simulations suggests that the ensemble of conformations of A1-LCD fluctuates among locally compact regions, globally compact conformations, and expanded conformations.
“Integrating SAXS and NMR measurements with simulations, suggests that the ensemble of conformations fluctuate among locally compact regions, globally compact conformations, and expanded conformations.88”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [88] source
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- Findingnone given
Many AlphaFold predictions feature regions of very low confidence, and these regions largely overlap with intrinsically disordered regions.
“Interestingly, many predictions feature regions of very low confidence, and these regions largely overlap with intrinsically disordered regions (IDRs).”
Quote in the paperNot a substantial claim - Findingcitation
The efficiency of T187 phosphorylation does not change monotonically with changes to Rg.
“However, the efficiency of T187 phosphorylation does not change monotonically with changes to R g .”
Quote in the paperSubstantial claim - Findingnone given
Roughly 30% of residues across predicted structures in the human proteome tend to have pLDDT scores less than 50.
“Roughly 30% of the residues across predicted structures in the human proteome tend to have pLDDT scores that are less than 50.”
Quote in the paperNot a substantial claim - Findingcitation
There is a cryptic motif that is proximal to the primary substrate motif that regulates the efficiency of T187 phosphorylation.
“Instead, there is a cryptic motif that is proxi-mal to the primary substrate motif that regulates the efficiency of T187 phosphorylation.64”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [64]
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- Findingown data
The Rg value computed using the very low confidence static structure excised from the AlphaFold prediction for A1-LCD is considerably higher than values obtained from direct measurements based on SAXS.
“The R g value we compute using the very low confidence static structure excised from the AlphaFold prediction is considerably higher than values obtained from direct measurements based on SAXS (Figure 2(C)).”
Quote in the paperSubstantial claim - Findingcitation
These conformational features of A1-LCD are driven by the distributed network of contacts formed between pairs of sequence-proximal or distal aromatic residues and influenced or diluted by the spacer regions that are interspersed between aromatic residues (stickers).
“These conformational features are driven by the distributed network of contacts formed between pairs of sequenceproximal or distal aromatic residues and influenced or diluted by the spacer regions that are interspersed between aromatic residues (stickers).88”
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- Findingnone given
The C-terminal domain of p27 (p27 CTD) generally shows low pLDDT scores (<70) in the AlphaFold prediction.
“The C-terminal domain of p27, p27 CTD , generally shows low pLDDT scores (<70) in the AlphaFold prediction.”
Quote in the paperNot a substantial claim - Findingcitation
The static AlphaFold structure likely overestimates the radius of gyration of IDRs as measured using SAXS.
“This is because, the static AlphaFold structure likely overestimates the radius of gyration of IDRs as measured using small angle X-ray scattering (SAXS) 64 (Figure 2(A)).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [64]
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- Findingnone given
For most of the PLD from hnRNP-A1 (residues 186-372), the AlphaFold prediction has a pLDDT score less than 50.
“For most of this region, the AlphaFold prediction has a pLDDT score that is less than 50.”
Quote in the paperSubstantial claim - Findingreasoning
The single static structure of p27 CTD predicted by AlphaFold suggests that this region is highly expanded, with few intramolecular contacts.
“The single static structure of p27 CTD predicted by AlphaFold suggests that this region is highly expanded, with few intramolecular contacts (Figure 2(B)).”
Quote in the paperNot a substantial claim - Findingown data
In most cases, the Rg values calculated using static structures from AlphaFold deviate from those obtained using experiments.
“In most cases, the R g values calculated using static structures from AlphaFold deviate from those obtained using experiments.”
Quote in the paperSubstantial claim - Findingnone given
Interactions between aromatic residues are essentially absent in the AlphaFold structure of A1-LCD.
“Interactions between aromatic residues are essentially absent in the AlphaFold structure.”
Quote in the paperSubstantial claim - Findingown data
The conformational ensemble of p27 CTD samples a large range of shapes and sizes.
“These ensembles show that the conformational ensemble of p27 CTD samples a large range of shapes and sizes.”
Quote in the paperSubstantial claim - Findingown data
Atomistic simulations show heterogeneous interactions between pairs of sequence-proximal or distal aromatic residues in A1-LCD.
“Highlighted are two representative conformations from atomistic simulations that show heterogeneous interactions between pairs of sequence-proximal or distal aromatic residues (black, space filling).”
Quote in the paperSubstantial claim - Interpretationreasoning
Given that residues are treated as an ideal gas with respect to the global frame of reference, the use of centrosymmetric potentials will lead to an isotropic expansion of the disordered regions that ended up with significant steric clashes during the process used to generate the penultimate structure.
“Further, given that the residues are treated as an ideal gas with respect to the global frame of reference, the use of centrosymmetric potentials will lead to an isotropic expansion of the disordered regions that ended up with significant steric clashes during the process used to generate the penultimate structure.”
Quote in the paperNot a substantial claim - Premisecitation
Although there are clear context dependent modulations of intrinsic sequence-ensemble relationships, these modulations range from being negligible to predictable based on the sequence features of IDRs and the types of folded domains to which IDRs are tethered.
“Although there are clear context dependent modulations of intrinsic sequence-ensemble relationships, these modulations range from being negligible to predictable based on the sequence features of IDRs and the types of folded domains to which IDRs are tethered.80,81”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning
The IDR does not behave as an inert tether that influences the radius of capture alone.
“Instead, closer scrutiny shows that the IDR does not behave as an inert tether that influences the radius of capture alone.”
Quote in the paperSubstantial claim - Premisecitation
Conservative estimates indicate that roughly 30% of sequences, 30 residues or longer, drawn at random from the human proteome, are likely to be intrinsically disordered regions.
“Conservative estimates indicate that roughly 30% of sequences, 30residues or longer, drawn at random from the human proteome, are likely to be IDRs. 3,5”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationreasoning
A vast majority of the very low confidence regions in AlphaFold predictions are likely to be intrinsically disordered, instead of being well-defined, autonomously foldable three-dimensional structures that AlphaFold fails at predicting.
“This implies that a vast majority of the very low confidence regions are likely to be intrinsically disordered, instead of being well-defined, autonomously foldable three-dimensional structures that AlphaFold fails at predicting.”
Quote in the paperSubstantial claim - Premisenone given
The C-terminal domain of p27, residues 96-198, remains disordered upon binding.
“In contrast, the C-terminal domain, residues 96-198, remains disordered upon binding.”
Quote in the paperSubstantial claim - Premisecitation
Many proteins with low complexity prion-like domains (PLDs) are drivers of phase separation.
“Many proteins with low complexity prion-like domains (PLDs) are drivers of phase separation.87”
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- Interpretationreasoning
The low, as opposed to very low, confidence score for p27 CTD is misleading.
“The low, as opposed to very low, confidence score is misleading in this case.”
Quote in the paperSubstantial claim - Premisecitation
AlphaFold, a deep learning-based approach to protein structure prediction, shows remarkable success in independent assessments of prediction accuracy.
“AlphaFold, a deep learning-based approach to protein structure prediction, shows remarkable success in independent assessments of prediction accuracy.”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationcitation
Cloud-like depictions for structures of IDRs are also likely to represent an artifact of allowing for steric clashes and the steps taken to alleviate these clashes.
“Additionally, the cloud-like depictions for structures of IDRs are also likely to represent an artifact of allowing for steric clashes and the steps taken to alleviate these clashes as deemed necessary.1”
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- Interpretationreasoning
A static structure either drawn at random from the ensemble or generated using a specific rendering or optimization procedure is neither a qualitative nor quantitative representation of conformational heterogeneity.
“Accordingly, a static structure either drawn at random from the ensemble or generated using a specific rendering or optimization procedure is neither a qualitative nor quantitative representation of conformational heterogeneity.”
Quote in the paperSubstantial claim - Interpretationreasoning
Poorly defined distance restraints within IDRs and between IDRs and folded domains likely result from poorer alignments of IDRs.
“This likely leads to poorly defined distance restraints within the IDRs and between the IDRs and the folded domains.”
Quote in the paperSubstantial claim - Study design and conductnone given
Detailed insights regarding the interactions that screen one another and the overall shapes, sizes, and local as well as global conformational fluctuations have emerged from atomistic simulations that were then vetted against experimental data.
“Detailed insights regarding the interactions that screen one another and the overall shapes, sizes, and local as well as global conformational fluctuations have emerged from atomistic simulations that were then vetted against experimental data.”
Quote in the paperNot a substantial claim - Interpretationcitation
Conformational clouds in AlphaFold predictions may arise from several aspects of the underlying methodology.
“it is worth noting that the conformational clouds one observes in AlphaFold predictions may arise from several aspects of the underlying methodology.1”
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- Premisecitation
pLDDT scores have been shown to be a competitive disorder predictor compared to standards in disorder prediction.
“pLDDT scores have been shown to be a competitive disorder predictor compared to standards in disorder prediction.5”
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- Interpretationcitation
In addition to being sequence-specific, the features of conformational ensembles can only be described in terms of single- or multi-parameter distribution functions and/or moments of these distributions.
“in addition to being sequence-specific, the features of conformational ensembles can only be described in terms of single-or multi-parameter distribution functions and/or moments of these distributions.79”
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- Interpretationreasoning
Together, these results suggest that p27 CTD samples a large range of sizes and shapes.
“Together, these results suggest that p27 CTD samples a large range of sizes and shapes.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Depictions of the space occupied by a disordered region, visual sense of contacts, or inferences regarding motif/residue accessibilities extracted using image processing should not be taken literally because such analyses have zero physical meaning.
“As a result, depictions of the space occupied by the disordered region, or a visual sense of contacts being formed, or inferences regarding motif/residue accessibilities extracted using image processing should not be taken literally because such analyses have zero physical meaning.”
Quote in the paperNot a substantial claim - Premisecitation
Httex1 has a clear preference for forming tadpole-like conformations.
“A curious feature of the conformational ensembles was the discovery that Httex1 has a clear preference for forming tadpole-like conformations.94”
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- Premisecitation
Many (not all) IDRs can undergo coupled folding and binding into context-specific three-dimensional structures.
“since many (not all) IDRs can undergo coupled folding and binding into context-specific threedimensional structures, 26,45”
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- Premisecitation
One of the challenges posed by IDRs stems from hypervariability of these regions across orthologs, making it difficult to uncover evolutionary constraints from alignments alone.
“one of the challenges posed by IDRs stems from hypervariability of these regions across orthologs, 57 making it difficult to uncover evolutionary constraints from alignments alone.58”
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- Interpretationcitation
These changes, as opposed to sharp conformational transitions as a function of polyQ length, are likely to influence the gain-of-function interactions that influence disease progression and neuronal death.
“These changes, as opposed to sharp conformational transitions as a function of polyQ length, are likely to influence the gain-of-function interactions that influence disease progression and neuronal death.”
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- Premisecitation
High-resolution structural studies of purely monomeric species are challenging because these molecules tend to self-associate readily.
“High-resolution structural studies of purely monomeric species are challenging because these molecules tend to selfassociate readily.89,90”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
The polyQ domain of Httex1 adopts globular conformations.
“The polyQ domain adopts globular conformations, wherein the radius of gyration scales as n 1/3 where n is the number of Gln residues in the polyQ tract.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [94] source
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- Premisecitation
One of the major insights leveraged by AlphaFold comes from the use of evolutionary covariations that can be extracted from large-scale multiple sequence alignments.
“One of the major insights leveraged by AlphaFold 1,2 comes from the use of evolutionary covariations that can be extracted from large-scale multiple sequence alignments.[49][50][51][52][53][54]”
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- Interpretationreasoning
Structural readouts are often confounded by polydisperse distributions of oligomers and higher-order assemblies.
“Therefore, structural readouts are often confounded by polydisperse distributions of oligomers and higher-order assemblies.”
Quote in the paperSubstantial claim - Premisecitation
Conformational heterogeneity of the Httex1 ensemble derives from the diversity of compact conformations within the polyQ domain and the distribution of internal distances and orientations that characterize the Pro-rich region.
“Conformational heterogeneity of this ensemble derives from the diversity of compact conformations within the polyQ domain and the distribution of internal distances and orientations that characterize the Pro-rich region.”
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- Premisecitation
Detailed atomistic descriptions of conformational ensembles enabled the development of a coarse-grained stickers-and-spacers model for simulations of A1-LCD phase behavior.
“Importantly, the detailed atomistic descriptions of conformational ensembles enabled the development of a coarse-grained stickers-and-spacers model for simulations of A1-LCD phase behavior.88”
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- Premisecitation
The radius of gyration of the polyQ domain scales as n^1/3, where n is the number of Gln residues in the polyQ tract.
“The polyQ domain adopts globular conformations, wherein the radius of gyration scales as n 1/3 where n is the number of Gln residues in the polyQ tract.”
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- The quote only partly states this claim. 2
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FindingcitationModulating the charge patterning changes the mean size of the conformational ensemble of p27 CTD monotonically, consistent with SAXS experiments.
“Modulating the charge patterning changes the mean size of the conformational ensemble monotonically, consistent with SAXS experiments.64”
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FindingcitationA sizable fraction of the N-terminal region of p27 is predicted to adopt a helical structure by AlphaFold, and this is consistent with experimental characterizations based on NMR spectroscopy.
“A sizable fraction of the N-terminal region is predicted to adopt a helical structure by Alpha-Fold, and this is consistent with experimental characterizations based on nuclear magnetic resonance (NMR) spectroscopy.85”
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Findingown dataAtomistic simulations reproduce the average Rg value measured using SAXS for p27 CTD.
“Atomistic simulations reproduce the average R g value measured using SAXS.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationThe ensemble of an IDR is sequence-specific, and the extent of heterogeneity and relative preferences of conformations within the ensemble depend on the primary sequence, solution conditions, and functional contexts.
“This ensemble is sequence-specific 30,31 and the extent of heterogeneity 36 as well as the relative preferences of conformations within the ensemble will depend on the primary sequence, solution conditions, and functional contexts.”
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Premisenone givenDisorder implies that a diverse conformational ensemble best describes the region of interest.
“Instead, disorder implies that a diverse conformational ensemble best describes the region of interest.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationThe N-terminal portion (residues 1-95) of p27 folds upon binding to Cdk2/cyclin A and this leads to kinase inhibition.
“The N-terminal portion (residues 1-95) folds upon binding to Cdk2/cyclin A and this leads to kinase inhibition.85,86”
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PremisecitationAlphaFold developers state that long regions with pLDDT < 50 adopt a readily identifiable ribbon-like appearance and should not be interpreted as structures but rather as a prediction of disorder.
“In the current dataset, long regions with pLDDT < 50 adopt a readily identifiable ribbon-like appearance, and should not be interpreted as structures but rather as a prediction of disorder.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationIntrinsically disordered regions often evolve more rapidly than ordered regions, and alignments of these regions are generally poorer and involve large gaps and extensions of gaps because orthologous IDRs can span vast sequence lengths.
“Intrinsically disordered regions often evolve more rapidly than ordered regions and thus alignments of these regions are generally poorer and involve large gaps and extensions of gaps because orthologous IDRs can span vast sequence lengths.9,23,58,60,[68][69][70]”
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PremisecitationAlleviation of steric clashes leads to a steep decrease in potential energy, and often the local minimum will be situated closest to the region of the steepest drop in energy.
“Alleviation of steric clashes leads to a steep decrease in the potential energy, and often the local minimum will be situated closest to the region of the steepest drop in energy.72,73”
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PremisecitationOver the past two decades, there has been growing recognition that the sequence-structure-function paradigm must be generalized to account for the role of conformational heterogeneity and conformational dynamics in protein function.
“Over the past two decades, there has been growing recognition that the sequence-structurefunction paradigm must be generalized to account for the role of conformational heterogeneity and conformational dynamics in protein function.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisenone givenAlphaFold was deployed to predict the structures of 98.5% of proteins in the human proteome.
“created quite a stir when it was deployed to predict the structures of 98.5% of proteins in the human proteome.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationAromatic residues function as cohesive motifs known as stickers that drive single chain compaction as well as phase separation of A1-LCD.
“leading to the postulate, tested through theory, computations, and experiments, that aromatic residues function as cohesive motifs known as stickers that drive single chain compaction as well as phase separation 88 -the latter through a network of intermolecular interactions.”
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PremisecitationUnder standard conditions used to study and characterize protein structures, IDPs/IDRs are defined by conformational heterogeneity, and the preference for heterogeneity is encoded in their amino acid sequences.
“Under standard conditions used to study and characterize protein structures, IDPs/IDRs are defined by conformational heterogeneity, and the preference for heterogeneity is encoded in their amino acid sequences.11,[29][30][31]”
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PremisecitationThe overall number of distinct conformations, conformational heterogeneity, and relative importance of different conformations within the ensemble are defined by a combination of sequence-encoded short- and long-range interactions as well as modulation by solution conditions.
“The overall number of distinct conformations in the ensemble, the conformational heterogeneity, in terms of features such as the sizes and shapes sampled, and the relative importance of different conformations within the ensemble are defined by a combination of sequence-encoded short-and long-range interactions 37,38 as well as the modulation of these interactions by solution conditions.39,40”
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PremisecitationPrediction engines are available to identify regions that undergo disorder-to-order, order-to-disorder, and disorder-to-disorder transitions upon binding.
“Importantly, prediction engines are also available to identify regions that undergo disorder-to-order, order-to-disorder, and disorder-to-disorder transitions upon binding.44”
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PremisecitationThe Pro-rich C-terminal region of Httex1 forms a semi-flexible tail.
“The Pro-rich C-terminal region forms a semi-flexible tail.”
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PremisecitationIDPs/IDRs are best defined by a heterogeneous ensemble of conformations.
“IDPs/IDRs are best defined by a heterogeneous ensemble of conformations.36”
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InterpretationcitationThe growth of the 'sticky head' with polyQ length mediates homotypic interactions and modulates heterotypic interactions in the cellular context.
“Taken together with complementary efforts focused on characterizing Httex1 phase behavior, the results obtained from multipronged studies of monomeric Httex1 predict that the growth of the “sticky head” with polyQ length mediates homotypic interactions and modulates heterotypic interactions in the cellular context.94”
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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?
AlphaFold successfully predicts natively disordered protein regions, and there is a correlation between decrease of pLDDT and propensity to be in a disordered region.
“Evidence in favor of this point of view is the successful prediction of natively disordered protein regions by AlphaFold and the correlation between the decrease of pLDDT and propensity to be in a disordered region [25].”
From Using AlphaFold to predict the impact of single mutations on protein stability and function (2023) · cites this paper as [25]
Like peptides, IDPs and IDRs are best viewed as sampling diverse conformational ensembles rather than one static conformation.
“like peptides, IDPs and IDRs are best thought of as sampling diverse conformational ensembles rather than a single static conformation42”
From The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins (2024) · cites this paper as [42]
Ruff et al found radius of gyration values for IDPs/IDR-containing proteins from static AF2 models deviate significantly from SAXS experimental values.
“Ruff et al showed that radius of gyration values of IDPs / IDR containing proteins calculated using static AF2 models significantly deviates from those experimentally obtained by small-angle X-ray scattering (SAXS)42”
From The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins (2024) · cites this paper as [42]
Preliminary studies suggest most targets with very low pLDDT (<50) are likely IDPs/IDRs rather than well-folded proteins AF2 fails to predict.
“Preliminary studies suggest that the majority of targets with very low-confidence score (pLDDT < 50) assigned by AF2 are likely to be IDPs / IDRs rather than well-folded structures that AF2 fails to predict42–44”
From The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins (2024) · cites this paper as [42]
Some groups used MD simulations to suggest pLDDT and PAE provide information about dynamics and disorder.
“Some groups have used MD simulations to suggest that pLDDT and PAE metrics provide information on dynamics and disorder42,65”
From The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins (2024) · cites this paper as [42]
For many proteins, a single static AF2 model does not adequately represent solution-state structures.
“Preliminary comparison of SAXS-derived versus AF calculated P(r) curves revealed that for many cases a static AF2 model does not adequately describe solution state structures42,72.”
From The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins (2024) · cites this paper as [42]
Data-driven approaches can hardly predict the structure of intrinsically disordered proteins.
“It is therefore not surprising that it was recently shown [214] that data-driven approaches can hardly predict the structure of so-called intrinsically disordered proteins”
From Quantum Computing for Molecular Biology** (2023) · cites this paper as [214]
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.
Two different references are numbered 26
MinorThe reference list assigns number 26 to both the Miskei et al. and Tóth-Petróczy et al. papers, making citations to reference 26 ambiguous.
“26. Miskei, M., Antal, C., Fuxreiter, M., (2016). FuzDB: database of fuzzy complexes, a tool to develop stochastic structure-function relationships for protein complexes and higher-order assemblies. Nucleic Acids Res., 45, D228- D235.”
“26. To ´th-Petro ´czy, A ´., Oldfield, C.J., Simon, I., Takagi, Y., Dunker, A.K., Uversky, V.N., et al., (2008). Malleable machines in transcription regulation: The mediator complex. PLoS Comput. Biol., 4, e1000243”
Cites
Highly accurate protein structure prediction with AlphaFold
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The molecular basis for cellular function of intrinsically disordered protein regions
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Conformational ensembles of the human intrinsically disordered proteome
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Using AlphaFold to predict the impact of single mutations on protein stability and function
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“Evidence in favor of this point of view is the successful prediction of natively disordered protein regions by AlphaFold and the correlation between the decrease of pLDDT and propensity to be in a disordered region [25].”
BackgroundThe AlphaFold Database of Protein Structures: A Biologist’s Guide
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- Authors
- Ruff, K. M., & Pappu, R. V.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Pappu, Rohit V.
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 433
- Issue
- 20
- Pages
- 167208
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W3195375135
- Semantic Scholar
- 960aaaa85d1de9f8e2490d872165b720e3d4b565
- Cited by
- 635
- References
- 103
- Citations by year
- 2026: 97 · 2025: 154 · 2024: 139 · 2023: 144 · 2022: 91 · 2021: 10
- FWCI
- 10.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Molecular Biology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- AlphaFold, intrinsically disordered regions, protein structure prediction, sequence-function relationships, conformational heterogeneity, protein dynamics, protein-protein interaction network
- MeSH terms
- Deep Learning, Animals, Humans, Models, Molecular, Protein Conformation, Protein Folding, Computational Biology, Proteome, 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.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.
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 ›
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