title: Side-Chain Conformational Preferences Govern Protein-Protein Interactions.
abstract: Protein secondary structures serve as geometrically constrained scaffolds for the display of key interacting residues at protein interfaces. Given the critical role of secondary structures in protein folding and the dependence of folding propensities on backbone dihedrals, secondary structure is expected to influence the identity of residues that are important for complex formation. Counter to this expectation, we find that a narrow set of residues dominates the binding energy in protein-protein complexes independent of backbone conformation. This finding suggests that the binding epitope may instead be substantially influenced by the side-chain conformations adopted. We analyzed side-chain conformational preferences in residues that contribute significantly to binding. This analysis suggests that preferred rotamers contribute directly to specificity in protein complex formation and provides guidelines for peptidomimetic inhibitor design.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Watkins
authors.affiliation: Center for Computational Biology, Simons Foundation , New York, New York 10010, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Bonneau
authors.forename: Paramjit S
authors.initials: PS
authors.lastname: Arora
mesh_terms: D019295:Computational Biology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D011506:Proteins