Property Map Collective Variable as a Useful Tool for a Force Field Correction

The accuracy of biomolecular simulations depends on the accuracy of an empirical molecular mechanics potential known as a force field: a set of parameters and expressions to estimate the potential from atomic coordinates. Accurate parametrization of force fields for small organic molecules is a challenge due to their high diversity. One of the possible approaches is to apply a correction to the existing force fields. Here, we propose an approach to estimate the density functional theory (DFT)-derived force field correction which is calculated during the run of molecular dynamics without significantly affecting its speed. Using the formula known as a property map collective variable, we approximate the force field correction by a weighted average of this force field correction calculated only for a small series of reference structures. To validate this method, we used seven AMBER force fields, and we show how it is possible to convert one force field to behave like the other one. We also present the force field correction for the important anticancer drug Imatinib as a use case example. Our method appears to be suitable for adjusting the force field for general drug-like molecules. We provide a pipeline that generates the correction; this pipeline is available at https://pmcvff-correction.cerit-sc.cz/.

Automated summary

This study proposes a method to estimate a correction for density functional theory-derived force fields during the run of molecular dynamics, without significantly impacting its speed. The correction is approximated by a weighted average of force field corrections calculated for a series of reference structures. This method allows for adjusting force fields to better suit specific needs.