Understanding the physical and chemical principles governing specificity and promiscuity in protein—protein binding is important both for understanding mechanisms of molecular recognition and for designing novel biomolecular systems. The goal of this project is to identify the frequencies of occurrence of structural moieties (e.g., side chains and backbones of individual residues) and differences in their energetic contributions within promiscuous and specific protein—protein interactions. To achieve this goal, we are testing multiple hypotheses; for example, we hypothesize that specific proteins, which selectively bind to only one partner, preferentially utilize side chains to mediate binding when compared to promiscuous proteins, which may utilize the structurally consistent backbone moieties more preferentially. Electrostatic contributions of the structural moieties toward binding are quantified using component analysis techniques within a continuum electrostatic framework that takes solvent effects into account. Van der Waals and surface burial contributions are also evaluated. Two sets of protein complexes, identified by the literature to be either promiscuous or specific, are being analyzed to test our hypotheses. Preliminary results suggest statistically significant differences between the contributions of certain structural moieties between the two sets.

Structural determinants of promiscuous and specific binding in protein—protein complexes using component analysis techniques

249th National Meeting (2015)

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