Evaluating CHARMM Additive and Drude Polarizable Force Fields Through QM/MM Computations of the Vibrational Stark Effect

Abstract

The proper description of the electric environment of macromolecules is a critical challenge for force field methods. To test and validate the CHARMM force field's ability to describe this electric environment combined QM/MM calculations have been used to calculate the vibrational Stark effect (VSE). The Stark effect refers to the characteristic shift of a specific vibrational frequency upon the introduction of an electric field. In this work, we develop a first principles methodology to compute Stark shifts using correlated electronic structure techniques and validate this approach by computing the Stark shift of a model VSE probe, acetonitrile, in several solvents. The solvent environment around the probe is sampled through 20 ns molecular dynamics simulations of each molecule surrounded by several hundred explicit solvent molecules. From these simulations, two hundred snapshots of the probe with the solvent environment are collected for the QM/MM analysis. Several QM/MM computational schemes are compared for calculating the vibrational spectrum of the VSE probe in the field created by the solvent molecules, which are treated as MM atoms with the CHARMM force field. From these computations, an average Stark shift is determined for each probe molecule and compared to experimental measurements. This information can be directly related to the electric field surrounding the probe molecule, and therefore may be used as a direct test of the ability of a force field to reproduce the electric field around those functional groups. Information from these calculations will act as the basis for additional optimization of the force field to more accurately represent the electric fields in macromolecules.