Detalle de: Inferring the microscopic surface energy of protein-protein interfaces from mutation data

Mutations at protein–protein recognition sites alter binding strength by altering the chemical nature of the interacting surfaces. We present a simple surface energy model, parameterized with empirical values, yielding mean energies of −48 cal mol −1 Å −2 for interactions between hydrophobic surfaces, −51 to −80 cal mol −1 Å −2 for surfaces of complementary charge, and 66–83 cal mol −1 Å −2 for electrostatically repelling surfaces, relative to the aqueous phase. This places the mean energy of hydrophobic surface burial at −24 cal mol −1 Å −2 . Despite neglecting configurational entropy and intramolecular changes, the model correlates with empirical binding free energies of a functionally diverse set of rigid‐body interactions ( r = 0.66). When used to rerank docking poses, it can place near‐native solutions in the top 10 for 37% of the complexes evaluated, and 82% in the top 100. The method shows that hydrophobic burial is the driving force for protein association, accounting for 50–95% of the cohesive energy. The model is available open‐source from http://life.bsc.es/pid/web/surface_energy/ and via the CCharpPPI web server http://life.bsc.es/pid/ccharppi/ . Proteins 2015; 83:640–650. © 2015 Wiley Periodicals, Inc.