Free energies of solvation in the context of protein folding: Implications for implicit and explicit solvent models. Issue 7 (12th November 2015)

• Record Type: Journal Article
• Authors: Cumberworth, Alexander; Bui, Jennifer M.; Gsponer, Jörg
• Is Part Of: Journal of computational chemistry. Volume 37:Issue 7(2016)
• Page Start: 629
• Page End: 640
• Publication Date: 2015-11-12
• Subjects: implicit solvent -- protein folding -- free energy -- solvation -- molecular dynamics; Chemistry -- Data processing -- Periodicals; 542.85
• DOI: 10.1002/jcc.24235
• Languages: English
• ISSNs: 0192-8651

Abstract

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 Δ Δ G solv 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 Δ Δ G solv 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. Abstract : This work compares changes in solvation free energy upon folding provided by several implicit solvent models and the TIP3P explicit solvent model. Inconsistencies of an unexpected magnitude were found across the models, which could only be corrected by using settings that were nonphysical or system‐specific.