Refinement of the Drude Polarizable Force Field for Hexose Monosaccharides: Capturing Ring Conformational Dynamics with Enhanced Accuracy

Overview

Journal J Chem Theory Comput

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2024 Oct 9

PMID 39383338

Authors

Chythra J N

Olgun Guvench

Alexander D MacKerell Jr

Takumi Yamaguchi

Sairam S Mallajosyula

Affiliations

Soon will be listed here.

Abstract

We present a revised version of the Drude polarizable carbohydrate force field (FF), focusing on refining the ring and exocyclic torsional parameters for hexopyranose monosaccharides. This refinement addresses the previously observed discrepancies between calculated and experimental NMR coupling values, particularly in describing ring dynamics and exocyclic rotamer populations within major hexose monosaccharides and their anomers. Specifically, α-MAN, β-MAN, α-GLC, β-GLC, α-GAL, β-GAL, α-ALT, β-ALT, α-IDO, and β-IDO were targeted for optimization. The optimization process involved potential energy scans (PES) of the ring and exocyclic dihedral angles computed using quantum mechanical (QM) methods. The target data for the reoptimization included PES of the inner ring dihedrals (C1-C2-C3-C4, C2-C3-C4-C5, C5-O5-C1-C2, C4-C5-O5-C1, O5-C1-C2-C3, C3-C4-C5-O5) and the exocyclic torsions, other than the pseudo ring dihedrals (O1-C1-O5-C5, O2-C2-C1-O5, and O4-C4-C5-O5) and hydroxyl torsions used in the previous parametrization efforts. These parameters, in conjunction with previously developed Drude parameters for hexopyranose monosaccharides, were validated against experimental observations, including NMR data and conformational energetics, in aqueous environments. The resulting polarizable model is shown to be in good agreement with a range of QM data, experimental NMR data, and conformational energetics of monosaccharides in aqueous solutions. This offers a significant improvement of the Drude carbohydrate force field, wherein the refinement enhances the accuracy of accessing the conformational dynamics of carbohydrates in biomolecular simulations.

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