Evidence of Conformational Selection Driving the Formation of Ligand Binding Sites in Protein-Protein Interfaces
Open accessAbstract
Many protein-protein interactions (PPIs) are compelling targets for drug discovery, and in a number of cases can be disrupted by small molecules. The main goal of this study is to examine the mechanism of binding site formation in the interface region of proteins that are PPI targets by comparing ligand-free and ligand-bound structures. To avoid any potential bias, we focus on ensembles of ligand-free protein conformations obtained by nuclear magnetic resonance (NMR) techniques and deposited in the Protein Data Bank, rather than on ensembles specifically generated for this study. The measures used for structure comparison are based on detecting binding hot spots, i.e., protein regions that are major contributors to the binding free energy. The main tool of the analysis is computational solvent mapping, which explores the surface of proteins by docking a large number of small "probe" molecules. Although we consider conformational ensembles obtained by NMR techniques, the analysis is independent of the method used for generating the structures. Finding the energetically most important regions, mapping can identify binding site residues using ligand-free models based on NMR data. In addition, the method selects conformations that are similar to some peptide-bound or ligand-bound structure in terms of the properties of the binding site. This agrees with the conformational selection model of molecular recognition, which assumes such pre-existing conformations. The analysis also shows the maximum level of similarity between unbound and bound states that is achieved without any influence from a ligand. Further shift toward the bound structure assumes protein-peptide or protein-ligand interactions, either selecting higher energy conformations that are not part of the NMR ensemble, or leading to induced fit. Thus, forming the sites in protein-protein interfaces that bind peptides and can be targeted by small ligands always includes conformational selection, although other recognition mechanisms may also be involved.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Evidence of conformational selection driving formation of ligand binding sites in protein-protein interfaces was shown in a study using NMR ensembles of ligand-free protein conformations.
“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.”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [502]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Berman, H. M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.235 · Cited by 40,196 · see citing works
In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., et al. (2004) · Science · doi:10.1126/science.1092472 · Cited by 4,661 · see citing works
Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain
Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J., & Pavletich, N. P. (1996) · Science · doi:10.1126/science.274.5289.948 · Cited by 2,206 · see citing works
The role of dynamic conformational ensembles in biomolecular recognition
Boehr, D. D., Nussinov, R., & Wright, P. E. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.232 · Cited by 2,008 · see citing works
A Hot Spot of Binding Energy in a Hormone-Receptor Interface
Clackson, T., & Wells, J. A. (1995) · Science · doi:10.1126/science.7529940 · Cited by 1,987 · see citing works
Reaching for high-hanging fruit in drug discovery at protein–protein interfaces
Wells, J. A., & McClendon, C. L. (2007) · Nature · doi:10.1038/nature06526 · Cited by 1,963 · see citing works
Structure of Bcl-x <sub>L</sub> -Bak Peptide Complex: Recognition Between Regulators of Apoptosis
Sattler, M., Liang, H., Nettesheim, D., Meadows, R. P., Harlan, J. E., Eberstadt, M., Yoon, H. S., Shuker, S. B., Chang, B. S., Minn, A. J., et al. (1997) · Science · doi:10.1126/science.275.5302.983 · Cited by 1,476 · see citing works
Recognition Dynamics Up to Microseconds Revealed from an RDC-Derived Ubiquitin Ensemble in Solution
Lange, O. F., Lakomek, N., Farès, C., Schroeder, G. F., Walter, K. F. A., Becker, S., Meiler, J., Grubmüller, H., Griesinger, C., & de Groot, B. L. (2008) · Science · doi:10.1126/science.1157092 · Cited by 1,044 · see citing works
PIPER: An FFT‐based protein docking program with pairwise potentials
Kozakov, D., Brenke, R., Comeau, S. R., & Vajda, S. (2006) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.21117 · Cited by 865 · see citing works
Self-citationCsermely, P., Palotai, R., & Nussinov, R. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.04.009 · Cited by 821 · see citing works
Unraveling hot spots in binding interfaces: progress and challenges
DeLano, W. L. (2002) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(02)00283-x · Cited by 767 · see citing works
BAX activation is initiated at a novel interaction site
Gavathiotis, E., Suzuki, M., Davis, M. L., Pitter, K., Bird, G. H., Katz, S. G., Tu, H.-C., Kim, H., Cheng, E. H.-Y., Tjandra, N., et al. (2008) · Nature · doi:10.1038/nature07396 · Cited by 700 · see citing works
Folding funnels and binding mechanisms
Ma, B., Kumar, S., Tsai, C.-J., & Nussinov, R. (1999) · Protein Engineering, Design and Selection · doi:10.1093/protein/12.9.713 · Cited by 594 · see citing works
Druggability Indices for Protein Targets Derived from NMR-Based Screening Data
Hajduk, P. J., Huth, J. R., & Fesik, S. W. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm049131r · Cited by 525 · see citing works
Brenke, R., Kozakov, D., Chuang, G., Beglov, D., Hall, D. R., Landon, M. R., Mattos, C., & Vajda, S. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp036 · Cited by 460 · see citing works
Self-citationTobi, D., & Bahar, İ. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507603102 · Cited by 380 · see citing works
Folding and binding cascades: Shifts in energy landscapes
Tsai, C.-J., Ma, B., & Nussinov, R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.18.9970 · Cited by 365 · see citing works
Predicting druggable binding sites at the protein–protein interface
Fuller, J. C., Burgoyne, N. J., & Jackson, R. M. (2008) · Drug Discovery Today · doi:10.1016/j.drudis.2008.10.009 · Cited by 311 · see citing works
FTSite: high accuracy detection of ligand binding sites on unbound protein structures
Ngan, C. H., Hall, D. R., Zerbe, B. S., Grove, L. E., Kozakov, D., & Vajda, S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr651 · Cited by 294 · see citing works
Self-citationLee, E. F., Czabotar, P. E., Smith, B. J., Deshayes, K., Zobel, K., Colman, P. M., & Fairlie, W. D. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402178 · Cited by 280 · see citing works
Targeting Protein–Protein Interactions for Therapeutic Intervention: A Challenge for the Future
Zinzalla, G., & Thurston, D. E. (2009) · Future Medicinal Chemistry · doi:10.4155/fmc.09.12 · Cited by 257 · see citing works
Discovery of a Potent Small Molecule IL-2 Inhibitor through Fragment Assembly
Braisted, A. C., Oslob, J. D., DeLano, W. L., Hyde, J., McDowell, R. S., Waal, N. D., Yu, C. H., Arkin, M. R., & Raimundo, B. C. (2003) · Journal of the American Chemical Society · doi:10.1021/ja034247i · Cited by 256 · see citing works
Locating and characterizing binding sites on proteins
Mattos, C., & Ringe, D. (1996) · Nature Biotechnology · doi:10.1038/nbt0596-595 · Cited by 256 · see citing works
Structural conservation of druggable hot spots in protein–protein interfaces
Kozakov, D., Hall, D. R., Chuang, G., Cencic, R., Brenke, R., Grove, L. E., Beglov, D., Pelletier, J., Whitty, A., & Vajda, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1101835108 · Cited by 245 · see citing works
Self-citationTransient Pockets on Protein Surfaces Involved in Protein−Protein Interaction
Eyrisch, S., & Helms, V. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm070095g · Cited by 212 · see citing works
How Well Can We Understand Large-Scale Protein Motions Using Normal Modes of Elastic Network Models?
Yang, L., Song, G., & Jernigan, R. L. (2007) · Biophysical Journal · doi:10.1529/biophysj.106.095927 · Cited by 206 · see citing works
Włodarski, T., & Žagrović, B. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906966106 · Cited by 194 · see citing works
PUMA binding induces partial unfolding within BCL-xL to disrupt p53 binding and promote apoptosis
Follis, A. V., Chipuk, J. E., Fisher, J. C., Yun, M., Grace, C. R., Nourse, A., Baran, K., Ou, L., Min, L., White, S. W., et al. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1166 · Cited by 174 · see citing works
Between a rock and a hard place?
Whitty, A., & Kumaravel, G. (2006) · Nature Chemical Biology · doi:10.1038/nchembio0306-112 · Cited by 170 · see citing works
Zhou, H. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2009.11.029 · Cited by 161 · see citing works
Inhibition of the p53-MDM2 Interaction: Targeting a Protein-Protein Interface
Chêne, P. (2004) · Molecular Cancer Research · doi:10.1158/1541-7786.20.2.1 · Cited by 152 · see citing works
A Comprehensive Survey of Small-Molecule Binding Pockets in Proteins
Gao, M., & Skolnick, J. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003302 · Cited by 142 · see citing works
Uhrı́nová, S., Uhrı́n, D., Powers, H., Watt, K., Zheleva, D. I., Fischer, P. M., McInnes, C., & Barlow, P. N. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.05.010 · Cited by 141 · see citing works
Inhibition of the p53-MDM2 interaction: targeting a protein-protein interface.
Chêne, P. (2004) · PubMed · Cited by 136 · see citing works
Ciulli, A., Williams, G., Smith, A. G., Blundell, T. L., & Abell, C. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm060490r · Cited by 135 · see citing works
Supramodular structure and synergistic target binding of the N-terminal tandem PDZ domains of PSD-95
Long, J., Tochio, H., Wang, P., Fan, J., Sala, C., Niethammer, M., Sheng, M., & Zhang, M. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(03)00113-x · Cited by 134 · see citing works
The structural basis of Edc3‐ and Scd6‐mediated activation of the Dcp1:Dcp2 mRNA decapping complex
Fromm, S. A., Truffault, V., Kamenz, J. L., Braun, J. E., Hoffmann, N. A., Izaurralde, E., & Sprangers, R. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.408 · Cited by 133 · see citing works
Computational mapping identifies the binding sites of organic solvents on proteins
Dennis, S., Körtvélyesi, T., & Vajda, S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.062398499 · Cited by 126 · see citing works
Self-citationMetz, A., Pfleger, C., Kopitz, H., Pfeiffer‐Marek, S., Baringhaus, K. H., & Gohlke, H. (2011) · Journal of Chemical Information and Modeling · doi:10.1021/ci200322s · Cited by 123 · see citing works
Lavi, A., Ngan, C. H., Movshovitz‐Attias, D., Bohnuud, T., Yueh, C., Beglov, D., Schueler‐Furman, O., & Kozakov, D. (2013) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.24422 · Cited by 118 · see citing works
Self-citationWinter, A., Higueruelo, A. P., Marsh, M., Sigurdardottir, A., Pitt, W. R., & Blundell, T. L. (2012) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583512000108 · Cited by 115 · see citing works
Characterization of protein-ligand interaction sites using experimental and computational methods.
Vajda, S., & Guarnieri, F. (2006) · PubMed · Cited by 109 · see citing works
Self-citationBucher, D., Grant, B. J., & McCammon, J. A. (2011) · Biochemistry · doi:10.1021/bi201481a · Cited by 100 · see citing works
Luca, L. D., Barreca, M. L., Ferro, S., Christ, F., Iraci, N., Gitto, R., Monforte, A., Debyser, Z., & Chimirri, A. (2009) · ChemMedChem · doi:10.1002/cmdc.200900070 · Cited by 100 · see citing works
Meireles, L., Gür, M., Bakan, A., & Bahar, İ. (2011) · Protein Science · doi:10.1002/pro.711 · Cited by 100 · see citing works
Wang, Y., Coulombe, R., Cameron, D. R., Thauvette, L., Massariol, M.-J., Amon, L. M., Fink, D., Titolo, S., Welchner, E., Yoakim, C., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311376200 · Cited by 98 · see citing works
Tsao, D. H. H., Sutherland, A. G., Jennings, L. D., Li, Y., Rush, T. S., Alvarez, J. C., Ding, W., Dushin, E. G., Dushin, R. G., Haney, S. A., et al. (2006) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2006.07.050 · Cited by 93 · see citing works
Johnson, D. K., & Karanicolas, J. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002951 · Cited by 92 · see citing works
TRAPP: A Tool for Analysis ofTransient BindingPockets inProteins
Kokh, D. B., Richter, S., Henrich, S., Czodrowski, P., Rippmann, F., & Wade, R. C. (2013) · Journal of Chemical Information and Modeling · doi:10.1021/ci4000294 · Cited by 77 · see citing works
Identification of Substrate Binding Sites in Enzymes by Computational Solvent Mapping
Silberstein, M., Dennis, S., Brown, L., Körtvélyesi, T., Clodfelter, K. H., & Vajda, S. (2003) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.08.019 · Cited by 75 · see citing works
Self-citationTargeting Specific PDZ Domains of PSD-95
Piserchio, A., Salinas, G. D., Li, T., Marshall, J. J., Spaller, M. R., & Mierke, D. F. (2004) · Chemistry & Biology · doi:10.1016/j.chembiol.2004.03.013 · Cited by 73 · see citing works
Ordering of the N-Terminus of Human MDM2 by Small Molecule Inhibitors
Michelsen, K., Jordan, J. B., Lewis, J. K., Long, A. M., Yang, E., Rew, Y., Zhou, J., Yakowec, P. S., Schnier, P. D., Huang, X. Y., et al. (2012) · Journal of the American Chemical Society · doi:10.1021/ja305839b · Cited by 71 · see citing works
Interplay of physics and evolution in the likely origin of protein biochemical function
Skolnick, J., & Gao, M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300011110 · Cited by 62 · see citing works
Charbonnier, S., Nominé, Y., Ramírez, J., Luck, K., Chappelle, A., Stote, R. H., Travé, G., Kieffer, B., & Atkinson, R. A. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.01.015 · Cited by 51 · see citing works
Grove, L. E., Hall, D. R., Beglov, D., Vajda, S., & Kozakov, D. (2013) · Bioinformatics · doi:10.1093/bioinformatics/btt102 · Cited by 34 · see citing works
Self-citationVértessy, B. G., & Orosz, F. (2010) · BioEssays · doi:10.1002/bies.201000068 · Cited by 31 · see citing works
Hocker, H. J., Rambahal, N., & Gorfe, A. A. (2014) · Journal of Chemical Information and Modeling · doi:10.1021/ci400474u · Cited by 17 · see citing works
Blundell, T. L., & Bolaños-García, V. M. (2009) · Cell Cycle · doi:10.4161/cc.8.22.10311 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kozakov, D., Grove, L. E., Hall, D. R., Bohnuud, T., Mottarella, S. E., Luo, L., Xia, B., Beglov, D., & Vajda, S. (2015) · Nature Protocols · doi:10.1038/nprot.2015.043 · Cited by 643 · see citing works
Self-citationWei, G., Xi, W., Nussinov, R., & Ma, B. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00562 · Cited by 436 · see citing works
Principles and Overview of Sampling Methods for Modeling Macromolecular Structure and Dynamics
Maximova, T., Moffatt, R., Ma, B., Nussinov, R., & Shehu, A. (2016) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004619 · Cited by 211 · see citing works
Adaptability of protein structures to enable functional interactions and evolutionary implications
Haliloǧlu, T., & Bahar, İ. (2015) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2015.07.007 · Cited by 125 · see citing works
Kozakov, D., Hall, D. R., Napoleon, R. L., Yueh, C., Whitty, A., & Vajda, S. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00586 · Cited by 111 · see citing works
Self-citationPushkaran, A. C., Nataraj, N., Nair, N., Götz, F., Biswas, R., & Mohan, C. G. (2015) · Journal of Chemical Information and Modeling · doi:10.1021/ci500734k · Cited by 83 · see citing works
Mahajan, S., & Sanejouand, Y. (2015) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.12.020 · Cited by 77 · see citing works
Computational approaches to investigating allostery
Schueler‐Furman, O., & Wodak, S. J. (2016) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2016.06.017 · Cited by 72 · see citing works
Lessons from Hot Spot Analysis for Fragment-Based Drug Discovery
Hall, D. R., Kozakov, D., Whitty, A., & Vajda, S. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.08.003 · Cited by 67 · see citing works
Self-citationRate Constants and Mechanisms of Protein–Ligand Binding
Pang, X., & Zhou, H. (2017) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-070816-033639 · Cited by 64 · see citing works
Kuenemann, M. A., Spérandio, O., Labbé, C. M., Lagorce, D., Miteva, M. A., & Villoutreix, B. O. (2015) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2015.02.006 · Cited by 61 · see citing works
Integrated structural biology to unravel molecular mechanisms of protein-RNA recognition
Schlundt, A., Tants, J., & Sattler, M. (2017) · Methods · doi:10.1016/j.ymeth.2017.03.015 · Cited by 58 · see citing works
Zhao, Z., Martin, C., Fan, R., Bourne, P. E., & Xie, L. (2016) · BMC Bioinformatics · doi:10.1186/s12859-016-0941-9 · Cited by 49 · see citing works
Are protein-protein interfaces special regions on a protein’s surface?
Tonddast-Navaei, S., & Skolnick, J. (2015) · The Journal of Chemical Physics · doi:10.1063/1.4937428 · Cited by 31 · see citing works
Lazou, M., Khan, O., Nguyen, T., Padhorny, D., Kozakov, D., Joseph‐McCarthy, D., & Vajda, S. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2412719121 · Cited by 31 · see citing works
Self-citationBorsatto, A., Gianquinto, E., Rizzi, V., & Gervasio, F. L. (2024) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.3c01318 · Cited by 28 · see citing works
Computational allosteric ligand binding site identification on Ras proteins
McCarthy, M. J., Prakash, P., & Gorfe, A. A. (2015) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmv100 · Cited by 28 · see citing works
Discovery of novel peptide neurotoxins from sea anemone species
Fu, J., Liao, Y., Jin, A., & Gao, B. (2021) · Frontiers in Bioscience-Landmark · doi:10.52586/5022 · Cited by 18 · see citing works
Ahmad, H. I., Afzal, G., Jamal, A., Kiran, S., Khan, M. A., Mehmood, K., Kamran, Z., Ahmed, I., Ahmad, S., Ahmad, A., et al. (2021) · BioMed Research International · doi:10.1155/2021/5574789 · Cited by 18 · see citing works
RetractedLiu, X., Jia, Z., & Chen, J. (2017) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.7b06768 · Cited by 17 · see citing works
Computational Solvent Mapping in Structure-Based Drug Design
Hall, D. R., & Enyedy, I. J. (2015) · Future Medicinal Chemistry · doi:10.4155/fmc.14.155 · Cited by 15 · see citing works
Considerations of Protein Subpockets in Fragment‐Based Drug Design
Bartolowits, M. D., & Davisson, V. J. (2015) · Chemical Biology & Drug Design · doi:10.1111/cbdd.12631 · Cited by 13 · see citing works
Belkin, S., Kundrotas, P. J., & Vakser, I. A. (2018) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-018-0124-z · Cited by 5 · see citing works
Pagán, O. R. (2024) · BioEssays · doi:10.1002/bies.202300195 · Cited by 4 · see citing works
Salomane, N., Mhlongo, N. N., Mokoena, F., Mafuna, T., & Simelane, M. B. C. (2025) · ChemistrySelect · doi:10.1002/slct.202404397 · Cited by 1 · see citing works
Activation and Inhibition of Biological Function through Design of Novel Protein-Ligand Interactions
Budiardjo, S. J. (2019) · KU ScholarWorks (The University of Kansas)
BindingDB Entry 50006473: New Frontiers in Druggability.
BindingDB (2020) · UC San Diego · doi:10.7270/q24t6nc6
- Authors
- Bohnuud, T., Kozakov, D., & Vajda, S.
- Affiliations
- Boston University (US)
- Corresponding author
- Kozakov, Dima
- ORCID
- Kozakov, Dima
- Venue
- PLoS Computational Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-10-02
- Volume
- 10
- Issue
- 10
- Pages
- e1003872
- ISSN
- 1553-734X (ISSN-L)
- 1553-7358
- PMC
- PMC4183424
- OpenAlex
- W2156244640
- Cited by
- 27
- References
- 58
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2021: 2 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 11
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Computational Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Science Foundation (1147082)
- National Institutes of Health (4r01gm061867-15)
- National Institute of General Medical Sciences (R01GM093147, R01GM064700, R01-GM061867, 1R01GM061867)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- conformational selection, protein-protein interaction, binding hot spots, induced fit, protein-peptide interactions, protein-ligand interactions, molecular recognition, binding free energy
- MeSH terms
- Binding Sites, Models, Molecular, Protein Binding, Protein Conformation, Proteins, Computational Biology, Nuclear Magnetic Resonance, Biomolecular, Databases, Protein
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.
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
