An improved GROMOS96 force field for aliphatic hydrocarbons in the condensed phase

Over the past 4 years the GROMOS96 force field has been successfully used i n biomolecular simulations, for example in peptide folding studies and deta iled protein investigations, but no applications to lipid systems have been published yet. Here we provide a detailed investigation of aliphatic liqui d systems. For liquids of larger aliphatic chains, n-heptane and longer, th e standard GROMOS96 parameter sets 43A1 and 43A2 yield a too low pressure a t the experimental density. Therefore, a reparametrization of the GROMOS96 force field regarding aliphatic carbons was initiated. The new force field parameter set 45A3 shows considerable improvements for n-alkanes, cyclo-, i so-, and neoalkanes and other branched aliphatics. Liquid densities and hea t of vaporization are reproduced for almost all of these molecules. Excelle nt agreement is found with experiment for the free energy of hydration for alkanes. The GROMOS96 45A3 parameter set should, therefore, be suitable for application to lipid aggregates such as membranes and micelles, for mixed systems of aliphatics with or without water, for polymers, and other apolar systems that may interact with different biomolecules. (C) 2001 John Wiley & Sons, Inc.