Assessment of Free Energies From Electrostatic Embedding Density Functional Tight Binding-Based/Molecular Mechanics in Periodic Boundary Conditions

Abstract

Electrostatic embedding quantum mechanics/molecular mechanics (QM/MM) methods in periodic boundary conditions (PBC) can successfully describe the condensed phase reactivity of a fragment treated at the QM level with an atomistic description of an electrostatic environment treated at the MM level. The computational cost of ab initio QM methods limits the phase space sampling, thus affecting statistical quantities like free energies. Here, we describe the implementation of a PBC-adapted QM/MM model based on the semi-empirical density-functional based tight-binding (DFTB) method within the GAMESS-US quantum package interfaced with Tinker. Further, we take advantage of the free energy methods provided by a newly developed interface with the PLUMED plugin. The versatility of the implementation is illustrated by the prediction of the free energy profile for three different families of reactions in solution. Overall, using the DFTB/MM, it has been possible to obtain results that are at least in a qualitatively agreement with respect to the experimental data or high-level ab initio simulations.