A simple physical model for binding energy hot spots in protein-protein complexes

TitleA simple physical model for binding energy hot spots in protein-protein complexes
Publication TypeJournal Article
Year of Publication2002
AuthorsKortemme, T., & Baker D.
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue22
Pagination14116-21
Date Published2002 Oct 29
ISSN0027-8424
KeywordsAlanine, Energy Transfer, Models, Molecular, Primary Publication, Protein Binding, Protein Conformation, Proteins, Water
Abstract

Protein-protein recognition plays a central role in most biological processes. Although the structures of many protein-protein complexes have been solved in molecular detail, general rules describing affinity and selectivity of protein-protein interactions do not accurately account for the extremely diverse nature of the interfaces. We investigate the extent to which a simple physical model can account for the wide range of experimentally measured free energy changes brought about by alanine mutation at protein-protein interfaces. The model successfully predicts the results of alanine scanning experiments on globular proteins (743 mutations) and 19 protein-protein interfaces (233 mutations) with average unsigned errors of 0.81 kcal/mol and 1.06 kcal/mol, respectively. The results test our understanding of the dominant contributions to the free energy of protein-protein interactions, can guide experiments aimed at the design of protein interaction inhibitors, and provide a stepping-stone to important applications such as interface redesign.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
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