Multipole models of sulphur for accurate anisotropic electrostatic interactions within force fields

Abstract

Nowadays, as computing has become much more available, a fresh momentum has been observed in the field of re-visioning and re-parameterizing the usual tools, as well as estimating for the incorporation of new qualitative capabilities, aimed at making more accurate and reliable predictions in drug discovery processes. Inspired by the success of modelling the electrostatic part of the halogen bonding (XB) by means of the distributed multipole expansion, a study is presented which attempts to extend this approach to a tougher case of σ-hole interaction: sulphur-based chalcogen bonding. To that end, 11 anisotropic models have been derived and tested for their performance in the reproduction of reference ab initio molecular electrostatic potential. A careful examination resulted in three models which have been selected for further examination as a part of the molecular mechanics force field (GAFF). The combined force field was used to estimate inter- and intra-molecular interactions for the molecular systems, capable of differentiating the binding from the σ-hole and other directions. The anisotropic models proposed were generally able to correct the wrong predictions of the sulphur models based only on isotropic charges and, thus, are a promising direction for further development of the refined electrostatics force fields.