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

• Published in: Proteins, structure, function, and bioinformatics Vol. 32; no. 2; pp. 129 - 135
• Main Authors: Martorana, V., Corongiu, G., Palma, M.U.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.08.1998
• Subjects: Amino Acids - chemistry; Animals; Aprotinin - chemistry; BPTI; Cattle; Chemical Phenomena; Chemistry, Physical; Computer Simulation; energy landscapes; funneling and recognition; hydration; Models, Chemical; molecular dynamics; PMF; Protein Conformation; Protein Folding; Solubility; solvent-induced forces; Thermodynamics; Water
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/(SICI)1097-0134(19980801)32:2<129::AID-PROT1>3.0.CO;2-G

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 diversified understanding of the role of hydrophobic/philic/charged groups in establishing the exquisite specificity of biomolecular folding and functional conformation. Its relevance is appreciated by noting that the work of a typical SIF acting on one residue, when displaced across a distance of 1 Å, is the equivalent of up to a few kcal/mol, which is the range of the stability/function free energy of a protein. Proteins 32:129–135, 1998. © 1998 Wiley‐Liss, Inc.