Atomic partial charge predictions for furanoses by random forest regression with atom type symmetry function

Abstract

Furanoses that are components for many important biomolecules have complicated conformational spaces due to the flexible ring and exo-cyclic moieties. Machine learning algorithms, which require descriptors as structural inputs, can be used to efficiently compute conformational adaptive (CA) charges to capture the electrostatic potential variations caused by the conformational changes in the molecular mechanics (MM) calculations. In the present study, we introduced atom type symmetry function (ATSF) developed based on atom centered symmetry function (ACSF) for describing conformations for furanoses, in which atoms were categorized by atom types defined by their properties or connectivity in classic molecular mechanics (MM) force field parameters to generate a suitable coordinate size. Random forest regression (RFR) models with ATSF showed improvements for predicting CA charges and dipole moments for furanoses compared to those with ACSF and atom name symmetry functions where atoms were categorized by their unique atom names. The CA charges predicted by RFR models with ATSF showed more comparable reproductions of the carbohydrate–water and carbohydrate–protein interactions computed with RESP charges individually derived from QM calculations than the ensemble-averaged atomic charge sets commonly employed in molecular mechanics force fields, suggesting that the predicted CA charges were capable of including electrostatic variations in their dynamic charge values. Improvements by ATSF showed that categorizing atoms by atom types introduced chemical structural perceptions to descriptors and produced a suitable coordinate size in ATSF to capture key structural features for furanoses. This categorizing scheme also allows ATSF to be readily adopted by other biomolecules thanks to the broad implementations of MM force fields.