Inferring the microscopic surface energy of protein-protein interfaces from mutation data
Rights accessOpen Access
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, parameterised with empirical DDG values, yielding mean energies of -48 cal.mol−1.°A−2 for interactions between hydrophobic surfaces, -51 to -80 cal.mol−1.°A −2 for surfaces of complementary charge, and 66 to 83 cal.mol−1.°A−2 for electrostatically repelling surfaces, relative to the aqueous phase. This places the mean energy of hydrophobic surface burial at -24 cal.mol−1.°A−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 opensource from http://life.bsc.es/pid/web/surface_energy/ and via the CCharpPPI web server http://life.bsc.es/pid/ccharppi/.
CitationMoal, Iain H.; Dapkūnas, Justas; Fernández-Recio, Juan. Inferring the microscopic surface energy of protein-protein interfaces from mutation data. "Proteins", Abril 2015, vol. 83, núm. 4, p. 640-650.