title: Variational Optimization of an All-Atom Implicit Solvent Force Field to Match Explicit Solvent Simulation Data.
abstract: The development of accurate implicit solvation models with low computational cost is essential for addressing many large-scale biophysical problems. Here, we present an efficient solvation term based on a Gaussian solvent-exclusion model (EEF1) for simulations of proteins in aqueous environment, with the primary aim of having a good overlap with explicit solvent simulations, particularly for unfolded and disordered states - as would be needed for multiscale applications. In order to achieve this, we have used a recently proposed coarse-graining procedure based on minimization of an entropy-related objective function to train the model to reproduce the equilibrium distribution obtained from explicit water simulations. Via this methodology, we have optimized both a charge screening parameter and a backbone torsion term against explicit solvent simulations of anα-helical and aβ-stranded peptide. The performance of the resulting effective energy function, termed EEF1-SB, is tested with respect to the properties of folded proteins, the folding of small peptides or fast-folding proteins, and NMR data for intrinsically disordered proteins. The results show that EEF1-SB provides a reasonable description of a wide range of systems, but its key advantage over other methods tested is that it captures very well the structure and dimension of disordered or weakly structured peptides. EEF1-SB is thus a computationally inexpensive (~ 10 times faster than Generalized-Born methods) and transferable approximation for treating solvent effects.
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark ; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, U.S.A. ; SISSA-Scuola Internazionale Superiore di Studi Avanzati,Trieste, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Bottaro
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark ; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, U.S.A.
authors.forename: Kresten
authors.initials: K
authors.lastname: Lindorff-Larsen
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom ; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, U.S.A.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Best
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