Interaction of explicit solvent with hydrophobic/philic/charged residues of a protein: Residue character vs. conformational context

Molecular dynamics simulations of model solutes in explicit molecular water have recently elicited novel aspects of the strong nonpair additivity of the potential of mean force (PMF) and related solvent-induced forces (SIFs) and hydration. Here we present the results of the same type of work on SIFs acting on bovine pancreatic trypsin inhibitor (BPTI) at single residue/sidechain resolution. In this system, nonpair additivity and the consequent dependence of SIFs on the protein conformational context are sufficiently strong to overturn SIFs on some individual residues, relative to expectations based on their individual characters. This finding calls for a revisitation and offers a richer and…