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 addit ivity 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 (BP TI) at single residue/sidechain resolution. In this system, nonpair ad ditivity and the consequent dependence of SIFs on the protein conforma tional context are sufficiently strong to overturn SIFs on some indivi dual residues, relative to expectations based on their individual char acters, This finding calls for a revisitation and offers a richer and diversified understanding of the role of hydrophobic/philic/charged gr oups in establishing the exquisite specificity of biomolecular folding and functional conformation. Its relevance is appreciated by noting t hat the work of a typical SIF acting on one residue, when displaced ac ross a distance of 1 Angstrom, is the equivalent of up to a few kcal/m ol, which is the range of the stability/function free energy of a prot ein. Proteins 32:129-135, 1998 (C) 1998 Wiley-Liss, Inc.