Refinement of the\nDrude Polarizable Force Field for\nHexose Monosaccharides: Capturing Ring Conformational Dynamics with\nEnhanced Accuracy

We present a revised version of the\nDrude polarizable\ncarbohydrate\nforce field (FF), focusing on refining the ring and exocyclic torsional\nparameters for hexopyranose monosaccharides. This refinement addresses\nthe previously observed discrepancies between calculated and experimental\nNMR <sup>3</sup><i>J</i> coupling values, particularly in\ndescribing ring dynamics and exocyclic rotamer populations within\nmajor hexose monosaccharides and their anomers. Specifically, α-MAN,\nβ-MAN, α-GLC, β-GLC, α-GAL, β-GAL, α-ALT,\nβ-ALT, α-IDO, and β-IDO were targeted for optimization.\nThe optimization process involved potential energy scans (PES) of\nthe ring and exocyclic dihedral angles computed using quantum mechanical\n(QM) methods. The target data for the reoptimization included PES\nof the inner ring dihedrals (C1–C2–C3–C4, C2–C3–C4–C5,\nC5–O5–C1–C2, C4–C5–O5–C1,\nO5–C1–C2–C3, C3–C4–C5–O5)\nand the exocyclic torsions, other than the pseudo ring dihedrals (O1–C1–O5–C5,\nO2–C2–C1–O5, and O4–C4–C5–O5)\nand hydroxyl torsions used in the previous parametrization efforts.\nThese parameters, in conjunction with previously developed Drude parameters\nfor hexopyranose monosaccharides, were validated against experimental\nobservations, including NMR data and conformational energetics, in\naqueous environments. The resulting polarizable model is shown to\nbe in good agreement with a range of QM data, experimental NMR data,\nand conformational energetics of monosaccharides in aqueous solutions.\nThis offers a significant improvement of the Drude carbohydrate force\nfield, wherein the refinement enhances the accuracy of accessing the\nconformational dynamics of carbohydrates in biomolecular simulations.