Why Computed Protein Folding Landscapes Are Sensitive to the Water Model.

ABSTRACT: We investigate the effect of solvent models on the computed thermodynamics of protein folding. Atomistic folding simulations of a fast-folding mini-protein, CLN025, were employed to compare two commonly used explicit solvent water models, TIP3P and TIP4P/Ew, and one implicit solvent (AMBER generalized Born) model. Although all three solvent models correctly identify the same native folded state (RMSD = 1.5 ± 0.1 Å relative to the experimental structure), the corresponding free energy landscapes vary drastically between water models: almost an order-of-magnitude difference is seen in the predicted fraction of the unfolded state between the two explicit solvent models, with even larger differences between the implicit and the explicit models. Quantitative arguments are presented for why the

SUBMITTER: Anandakrishnan R 

PROVIDER: S-EPMC11560320 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature