Free energies of solvation in the context of protein folding: Implications for implicit and explicit solvent models

摘要

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 of several fast folding proteins are calculated from previously run s-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 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 parametersthe internal dielectric constant for the polar term and the surface tension coefficient for the nonpolar termthat were system-specific or physically unrealistic. We discuss the potential implications of our findings for both implicit and explicit solvent simulations. (c) 2015 Wiley Periodicals, Inc.