Side-chain conformational entropy at protein-protein interfaces

Christian Cole, Jim Warwicker

    Research output: Contribution to journalArticlepeer-review


    Protein-protein interactions are the key to many biological processes. How proteins selectively and correctly associate with their required protein partner(s) is still unclear. Previous studies of this "protein-docking problem" have found that shape complementarity is a major determinant of interaction, but the detailed balance of energy contributions to association remains unclear. This study estimates side-chain conformational entropy (per unit solvent accessible area) for various protein surface regions, using a self-consistent mean field calculation of rotamer probabilities. Interfacial surface regions were less flexible than the rest of the protein surface for calculations with monomers extracted from homodimer datasets in 21 of 25 cases, and in 8 of 9 for the large protomer from heterodimer datasets. In surface patch analysis, based on side-chain conformational entropy, 68% of true interfaces were ranked top for the homodimer set and 66% for the large protomer/heterodimer set. The results indicate that addition of a side-chain entropic term could significantly improve empirical calculations of protein-protein association.
    Original languageEnglish
    Pages (from-to)2860-2870
    Number of pages10
    JournalProtein science
    Issue number12
    Publication statusPublished - 1 Dec 2002


    • Conformational entropy
    • Dimerization
    • Protein-protein interactions
    • Rotamers


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