title: Role of solvation in pressure-induced helix stabilization.
abstract: In contrast to the well-known destabilization of globular proteins by high pressure, recent work has shown that pressure stabilizes the formation of isolated α-helices. However, all simulations to date have obtained a qualitatively opposite result within the experimental pressure range. We show that using a protein force field (Amber03w) parametrized in conjunction with an accurate water model (TIP4P/2005) recovers the correct pressure-dependence and an overall stability diagram for helix formation similar to that from experiment; on the other hand, we confirm that using TIP3P water results in a very weak pressure destabilization of helices. By carefully analyzing the contributing factors, we show that this is not merely a consequence of different peptide conformations sampled using TIP3P. Rather, there is a critical role for the solvent itself in determining the dependence of total system volume (peptide and solvent) on helix content. Helical peptide structures exclude a smaller volume to water, relative to non-helical structures with both the water models, but the total system volume for helical conformations is higher than non-helical conformations with TIP3P water at low to intermediate pressures, in contrast to TIP4P/2005 water. Our results further emphasize the importance of using an accurate water model to study protein folding under conditions away from standard temperature and pressure.
authors.affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Best
authors.affiliation: Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, Pennsylvania 18015, USA.
authors.forename: Cayla
authors.initials: C
authors.lastname: Miller
authors.affiliation: Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, Pennsylvania 18015, USA.
authors.forename: Jeetain
authors.initials: J
authors.lastname: Mittal
mesh_terms: D010455:Peptides / Q000737:chemistry*; D011312:Pressure; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D010455:Peptides; D014867:Water