Department of Chemistry, Indian Institute of Technology Gandhinagar, Gandhinagar, Gujarat India - 382355.
Department of Pharmaceutical Sciences and Administration, School of Pharmacy, University of New England, 716 Stevens Avenue, Portland, Maine 04103, United States.
J Chem Theory Comput. 2024 Oct 22;20(20):9161-9177. doi: 10.1021/acs.jctc.4c00656. Epub 2024 Oct 9.
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.
我们提出了一个经过修正的 Drude 可极化碳水化合物力场（FF），重点是改进六元吡喃糖单糖的环和非环扭转参数。这种改进旨在解决以前观察到的计算和实验 NMR 偶合值之间的差异，特别是在描述主要六元单糖及其差向异构体的环动力学和非环构象体分布方面。具体来说，针对 α-MAN、β-MAN、α-GLC、β-GLC、α-GAL、β-GAL、α-ALT、β-ALT、α-IDO 和 β-IDO 进行了优化。优化过程涉及使用量子力学（QM）方法计算的环和非环二面角的势能扫描（PES）。重新优化的目标数据包括内环二面角（C1-C2-C3-C4、C2-C3-C4-C5、C5-O5-C1-C2、C4-C5-O5-C1、O5-C1-C2-C3 和 C3-C4-C5-O5）和非环扭转的 PES，除了以前参数化工作中使用的伪环二面角（O1-C1-O5-C5、O2-C2-C1-O5 和 O4-C4-C5-O5）和羟基扭转。这些参数与以前开发的六元吡喃糖单糖的 Drude 参数一起，在水相环境中针对实验观察结果进行了验证，包括 NMR 数据和构象能。结果表明，该可极化模型与一系列 QM 数据、实验 NMR 数据和单糖在水溶液中的构象能非常吻合。这是对 Drude 碳水化合物力场的重大改进，其中改进提高了在生物分子模拟中访问碳水化合物构象动力学的准确性。
