Improvement of the Force Field for β-d-Glucose with Machine Learning

While the construction of a dependable force field for performing classical molecular dynamics (MD) simulation is crucial for elucidating the structure and function of biomolecular systems, the attempts to do this for glycans are relatively sparse compared to those for proteins and nucleic acids. Currently, the use of GLYCAM06 force field is the most popular, but there have been a number of concerns about its accuracy in the systematic description of structural changes. In the present work, we focus on the improvement of the GLYCAM06 force field for β-d-glucose, a simple and the most abundant monosaccharide molecule, with the aid of machine learning techniques implemented with the TensorFlow library. Following the pre-sampling over a wide range of configuration space generated by MD simulation, the atomic charge and dihedral angle parameters in the GLYCAM06 force field were re-optimized to accurately reproduce the relative energies of β-d-glucose obtained by the density functional theory (DFT) calculations according to the structural changes. The validation for the newly proposed force-field parameters was then carried out by verifying that the relative energy errors compared to the DFT value were significantly reduced and that some inconsistencies with experimental (e.g., NMR) results observed in the GLYCAM06 force field were resolved relevantly.