V.Helms and R.C.Wade, J.Comp.Chem. (1997) 18, 449-462.
European Molecular Biology Laboratory, Heidelberg, Germany
Four commonly-used molecular mechanics force fields, CHARMM22, OPLS, CVFF and GROMOS87, are compared for their ability to reproduce experimental free energies of hydration (DCSGhydr) from molecular dynamics (MD) simulations for a set of small non polar and polar organic molecules: propane, cyclo-propane, dimethyl-ether and acetone. DCSGhydrs were calculated by multiconfiguration thermodynamic integration for each of the different force fields with three different sets of partial atomic charges: full charges from an electrostatic potential fit (ESP) and ESP charges scaled by 0.8 and 0.6. All force fields, except for GROMOS87, give reasonable results for DCSGhydr if partial atomic charges of appropriate magnitude are assigned. For GROMOS87, the agreement with experiment for hydrocarbons (propane and ethane) was improved considerably by modifying the repulsive part of the carbon-water oxygen LJ potential. The small molecules studied are related to the chemical moieties constituting camphor (C10H16O). By invoking force field transferability, we calculated the DCSGhydr for camphor. With the modified GROMOS force field, a DCSGhydr within 4 kJ/mol of the experimental value of -14.8 kJ/mol was obtained. Camphor is one of the largest molecules for which an absolute hydration free energy has been calculated by molecular simulation. The accuracy and reliability of the thermodynamic integration calculations were analysed in detail and we found that, for DCSGhydr calculations for the set of small molecules in aqueous solution, MD simulations of 0.8 - 1.0 ns length give an upper statistical error bound of 1.5 kJ/mol, whereas shorter simulations of 0.25 ns length give an upper statistical error bound of 3.5 kJ/mol.
J.Comp.Chem. (1997) 18, 449-462.
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