Data-Driven Mapping of Gas-Phase Quantum Calculations to General Force Field Lennard-Jones Parameters

Molecular dynamics simulations are helpful tools for a range of applications, ranging from drug discovery to protein structure determination. The successful use of this technology largely depends on the potential function, or force field, used to determine the potential energy at each configuration of the system. Most force fields encode all of the relevant parameters to be used in distinct atom types, each associated with parameters for all parts of the force field, typically bond stretches, angle bends, torsions, and nonbonded terms accounting for van der Waals and electrostatic interactions. Much attention has been paid to the nonbonded parameters and their derivation, which are important in particular due to their governance of noncovalent interactions, such as protein-ligand binding. Parametrization involves adjusting the nonbonded parameters to minimize the error between simulation results and experimental properties, such as heats of vaporization and densities of neat liquids. In this setting, determining the best set of atom types is far from trivial, and the large number of parameters to be fit for the atom types in a typical force field can make it difficult to approach a true optimum. Here, we utilize a previously described Minimal Basis Iterative Stockholder (MBIS) method to carry out an atoms-in-molecules partitioning of electron densities. Information from these atomic densities is then mapped to Lennard-Jones parameters using a set of mapping parameters much smaller than the typical number of atom types in a force field. This approach is advantageous in two ways: it eliminates atom types by allowing each atom to have unique Lennard-Jones parameters, and it greatly reduces the number of parameters to be optimized. We show that this approach yields results comparable to those obtained with the typed GAFF 1.7 force field, even when trained on a relatively small amount of experimental data.