Improved Lennard-Jones Parameters for Accurate Molecular Dynamics Simulations

Abstract

The outcome of molecular dynamics simulation highly depends on the quality of the force field parameters used. While bonded and electrostatic parameters can be obtained automatically using gas phase quantum mechanical computations, the van der Waals parameters need systematic parameterization against experimental liquid phase data. In most cases, those parameters haven't been significantly refined since the early parameterization of additive force fields and their improvement appears as a mandatory step toward the development of a more accurate model.We collected the density, the heat of vaporization, and the solvation free energies of more than 500 compounds from experimental data. Those molecules were carefully picked to encompass all types of atomic van der Waals parameters for C, H, N, O, S, P, F, Cl and Br which are commonly used to simulate biomolecular systems and for drug design. As a starting point, we used the Lennard-Jones parameters of the General Amber Force Field (GAFF) as well as their bond and angle terms. The electrostatic and dihedral terms where reparameterized using the General Automated Atomic Model Parameterization (GAAMP). We ran liquid and gas phase simulations of the selected compounds to compute the different properties and optimize parameters by using analytical first derivatives of density and heat of vaporization. The solvation free energies will then be used for validation.Significant improvement on the prediction of the different experimental properties could be obtained. Further more, we could determine two additional atom types in order to reproduce experimental data more accurately. The parameters will be made globally accessible through the GAAMP web server and efforts are put into place to extend this approach to the Drude oscillator polarizable force field.