A biomolecular force field based on the free enthalpy of hydration and solvation: The GROMOS force‐field parameter sets 53A5 and 53A6

TLDR

The GROMOS force field has been repeatedly reparameterized to improve agreement with experimental data, driven by increasing computational power and the importance of accurately reproducing free enthalpies of hydration and solvation for biomolecular processes. Here we report the results of the latest, extensive reparameterization of the GROMOS force field. The new 53A5 and 53A6 parameter sets were derived by fitting to thermodynamic properties of small polar liquids and solvation free enthalpies of amino acid analogs in cyclohexane, then adjusting partial charges to match hydration free enthalpies in water. The resulting 53A5 and 53A6 sets are fully documented, with their differences from earlier versions highlighted. © 2004 Wiley Periodicals, Inc.

Abstract

Successive parameterizations of the GROMOS force field have been used successfully to simulate biomolecular systems over a long period of time. The continuing expansion of computational power with time makes it possible to compute ever more properties for an increasing variety of molecular systems with greater precision. This has led to recurrent parameterizations of the GROMOS force field all aimed at achieving better agreement with experimental data. Here we report the results of the latest, extensive reparameterization of the GROMOS force field. In contrast to the parameterization of other biomolecular force fields, this parameterization of the GROMOS force field is based primarily on reproducing the free enthalpies of hydration and apolar solvation for a range of compounds. This approach was chosen because the relative free enthalpy of solvation between polar and apolar environments is a key property in many biomolecular processes of interest, such as protein folding, biomolecular association, membrane formation, and transport over membranes. The newest parameter sets, 53A5 and 53A6, were optimized by first fitting to reproduce the thermodynamic properties of pure liquids of a range of small polar molecules and the solvation free enthalpies of amino acid analogs in cyclohexane (53A5). The partial charges were then adjusted to reproduce the hydration free enthalpies in water (53A6). Both parameter sets are fully documented, and the differences between these and previous parameter sets are discussed. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1656–1676, 2004