A structure‐based benchmark for protein–protein binding affinity
Open Access
- 6 January 2011
- journal article
- research article
- Published by Wiley in Protein Science
- Vol. 20 (3), 482-491
- https://doi.org/10.1002/pro.580
Abstract
We have assembled a nonredundant set of 144 protein–protein complexes that have high‐resolution structures available for both the complexes and their unbound components, and for which dissociation constants have been measured by biophysical methods. The set is diverse in terms of the biological functions it represents, with complexes that involve G‐proteins and receptor extracellular domains, as well as antigen/antibody, enzyme/inhibitor, and enzyme/substrate complexes. It is also diverse in terms of the partners' affinity for each other, with Kd ranging between 10−5 and 10−14M. Nine pairs of entries represent closely related complexes that have a similar structure, but a very different affinity, each pair comprising a cognate and a noncognate assembly. The unbound structures of the component proteins being available, conformation changes can be assessed. They are significant in most of the complexes, and large movements or disorder‐to‐order transitions are frequently observed. The set may be used to benchmark biophysical models aiming to relate affinity to structure in protein–protein interactions, taking into account the reactants and the conformation changes that accompany the association reaction, instead of just the final product.Keywords
Funding Information
- Indo-French Centre for the Promotion of Advanced Research (4003-2)
- NIH (R01 GM084884)
- The Netherlands Organization for Scientific Research (VICI Grant) (700.56.442)
- Cancer Research UK
This publication has 67 references indexed in Scilit:
- Are Scoring Functions in Protein−Protein Docking Ready To Predict Interactomes? Clues from a Novel Binding Affinity BenchmarkJournal of Proteome Research, 2010
- Quantitative prediction of protein–protein binding affinity with a potential of mean force considering volume correctionProtein Science, 2009
- Protein–protein interaction and quaternary structureQuarterly Reviews of Biophysics, 2008
- A novel empirical free energy function that explains and predicts protein–protein binding affinitiesBiophysical Chemistry, 2007
- A simple reference state makes a significant improvement in near‐native selections from structurally refined docking decoysProteins-Structure Function and Bioinformatics, 2007
- A Knowledge-Based Energy Function for Protein−Ligand, Protein−Protein, and Protein−DNA ComplexesJournal of Medicinal Chemistry, 2005
- NEW EMBO MEMBER'S REVIEW: Diversity of protein-protein interactionsThe EMBO Journal, 2003
- The Protein Data BankActa Crystallographica Section D-Biological Crystallography, 2002
- Principles of protein-protein interactions.Proceedings of the National Academy of Sciences of the United States of America, 1996
- Calculation of the free energy of association for protein complexesProtein Science, 1992