Dynamics Govern Specificity of a Protein-Protein Interface: Substrate Recognition by Thrombin.

ABSTRACT: Biomolecular recognition is crucial in cellular signal transduction. Signaling is mediated through molecular interactions at protein-protein interfaces. Still, specificity and promiscuity of protein-protein interfaces cannot be explained using simplistic static binding models. Our study rationalizes specificity of the prototypic protein-protein interface between thrombin and its peptide substrates relying solely on binding site dynamics derived from molecular dynamics simulations. We find conformational selection and thus dynamic contributions to be a key player in biomolecular recognition. Arising entropic contributions complement chemical intuition primarily reflecting enthalpic interaction patterns. The paradigm "dynamics govern specificity" might provide direct guidance for the identif

SUBMITTER: Fuchs JE 

PROVIDER: S-EPMC4619833 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature