Side-Chain Conformational Preferences Govern Protein-Protein Interactions

Andrew M. Watkins, Richard Bonneau, Paramjit Arora

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)10386-10389
Number of pages4
JournalJournal of the American Chemical Society
Volume138
Issue number33
DOIs
StatePublished - Aug 24 2016

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Proteins
Conformations
Peptidomimetics
Secondary Protein Structure
Protein Folding
Epitopes
Protein folding
Scaffolds (biology)
Binding energy
Scaffolds
Guidelines
Display devices

ASJC Scopus subject areas

  • Catalysis
  • Biochemistry
  • Chemistry(all)
  • Colloid and Surface Chemistry

Cite this

Side-Chain Conformational Preferences Govern Protein-Protein Interactions. / Watkins, Andrew M.; Bonneau, Richard; Arora, Paramjit.

In: Journal of the American Chemical Society, Vol. 138, No. 33, 24.08.2016, p. 10386-10389.

Research output: Contribution to journalArticle

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