Volume-based solvation models out-perform area-based models in combined studies of wild-type and mutated protein-protein interfa

Background: Empirical binding models have previously been investigated for the energetics of protein complexation (G models) and for the influence of mutations on complexation (i.e. differences between wild-type and mutant complexes, G models). We construct binding models to directly compare these processes, which have generally been studied separately. Results: Although reasonable fit models were found for both G and G cases, they differ substantially. In a dataset curated for the absence of mainchain rearrangement upon binding, nonpolar area burial is a major determinant of G models. However this G model does not fit well to the data for binding differences upon mutation. Burial of non-polar area is weighted down in fitting of G models. These calculations were made with no repacking of sidechains upon complexation, and only minimal packing upon mutation. We investigated the consequences of more extensive packing changes with a modified mean-field packing scheme. Rather than emphasis...

• Type: Journal
• Year: 2008
• Where: BMCBI
• Authors: Salim Bougouffa, Jim Warwicker
• Keywords: Binding Models, BMCBI 2008, Mutations, Solvent Accessible Area