Force Field Benchmark of Amino Acids: I. Hydration and Diffusion in Different Water Models

摘要: Thermodynamic and kinetic properties are of critical importance for the applicability computational models to biomolecules such as proteins. Here we present an extensive evaluation Amber ff99SB-ILDN force field modeling hydration diffusion amino acids with three-site (SPC, SPC/E, SPC/Eb, TIP3P), four-site (TIP4P, TIP4P-Ew, TIP4P/2005), five-site (TIP5P TIP5P-Ew) water models. Hydration free energies (HFEs) neutral acid side chain analogues have little dependence on model, a root-mean-square error (RMSE) ∼1 kcal/mol from experimental observations. On basis number interacting sites in HFEs charged chains can be putatively classified into three groups, which group lies between those four- models; each group, model is greatly eliminated when solvent Galvani potential considered. Some discrepancies location first peak ( RRDF) ion-water radial distribution function calculated observations were detected, systematic underestimation acetate (Asp chain) ion. The RMSE coefficients experiment increases linearly increasing at infinite dilution. TIP3P has fastest diffusivity, line literature findings, while "FB" "OPC" families well TIP4P/2005 perform well, within relative 5%, yields most accurate estimate coefficient. All tested overestimate by approximately 40% (TIP4P/2005) 200% (TIP3P). Scaling protein-water interactions ff99SBws ff03ws fields leads more negative but influence acids. recent FF/water combinations ff14SB/OPC3, ff15ipq/SPC/Eb, fb15/TIP3P-FB do not show obvious improvements accuracy quantities. These findings here establish benchmark that may aid development improvement classical accurately protein dynamics thermodynamics.