On hidden anisotropy of formally charged fragments

The proper and precise reproduction of the molecular electrostatic potential (MEP) is crucial to describe correctly electrostatic interactions in molecular modeling. Most of the classical molecular mechanics force fields for biomolecules and drug-like molecules use the atom-centered point charges to describe MEP. However, it has been systematically pointed out in literature that such an approximation is not always enough, and some groups, like amino group or heavy halogens, require the use of anisotropic model for better description of their MEP. At the same time, the formally charged groups have not been as extensively and systematically studied as their neutral counterparts. In this report, we demonstrate that the anisotropic models for formally charged groups do bring improvements in the reference MEP reproduction, that are comparable in magnitude to those for neutral groups.

Automated summary

The accurate reproduction of molecular electrostatic potential (MEP) is crucial for describing electrostatic interactions in molecular modeling. Most classical molecular mechanics force fields use atom-centered point charges to describe MEP, but it has been pointed out that this approximation is not always sufficient. Anisotropic models have been proposed for better describing MEP of groups such as amino and heavy halogens. This report demonstrates that anisotropic models for formally charged groups can bring improvements in MEP reproduction, comparable to those for neutral groups.