title: Free energies of solvation in the context of protein folding: Implications for implicit and explicit solvent models.
abstract: Implicit solvent models for biomolecular simulations have been developed to use in place of more expensive explicit models; however, these models make many assumptions and approximations that are likely to affect accuracy. Here, the changes in free energies of solvation upon folding ΔΔGsolv of several fast folding proteins are calculated from previously run μs-ms simulations with a number of implicit solvent models and compared to the values needed to be consistent with the explicit solvent model used in the simulations. In the majority of cases, there is a significant and substantial difference between the ΔΔGsolv values calculated from the two approaches that is robust to the details of the calculations. These differences could only be remedied by selecting values for the model parameters-the internal dielectric constant for the polar term and the surface tension coefficient for the nonpolar term-that were system-specific or physically unrealistic. We discuss the potential implications of our findings for both implicit and explicit solvent simulations. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Center for High-Throughput Biology, UBC, Vancouver, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Cumberworth
authors.affiliation: Center for High-Throughput Biology, UBC, Vancouver, Canada.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Bui
authors.affiliation: Center for High-Throughput Biology, UBC, Vancouver, Canada.
authors.forename: Jörg
authors.initials: J
authors.lastname: Gsponer
mesh_terms: D003198:Computer Simulation; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D009842:Oligopeptides; D010455:Peptides; D012997:Solvents; C506175:chignolin
keywords: free energy; implicit solvent; molecular dynamics; protein folding; solvation