Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA.
J Comput Chem. 2011 Dec;32(16):3339-53. doi: 10.1002/jcc.21873. Epub 2011 Sep 7.
N-Acetyl-β-glucosamine (NAG) is an important moiety of glycoproteins and is involved in many biological functions. However, conformational and dynamical properties of NAG molecules in aqueous solution, the most common biological environment, remain ambiguous due to limitations of experimental methods. Increasing efforts are made to probe structural properties of NAG and NAG-containing macromolecules, like peptidoglycans and polymeric chitin, at the atomic level using molecular dynamics simulations. In this work, we develop a polarizable carbohydrate force field for NAG and contrast simulation results of various properties using this novel force field and an analogous nonpolarizable (fixed charge) model. Aqueous solutions of NAG and its oligomers are investigated; we explore conformational properties (rotatable bond geometry), electrostatic properties (dipole moment distribution), dynamical properties (self-diffusion coefficient), hydrogen bonding (water bridge structure and dynamics), and free energy of hydration. The fixed-charge carbohydrate force field exhibits deviations from the gas phase relative rotation energy of exocyclic hydroxymethyl side chain and of chair/boat ring distortion. The polarizable force field predicts conformational properties in agreement with corresponding first-principles results. NAG-water hydrogen bonding pattern is studied through radial distribution functions (RDFs) and correlation functions. Intermolecular hydrogen bonding between solute and solvent is found to stabilize NAG solution structures while intramolecular hydrogen bonds define glycosidic linkage geometry of NAG oligomers. The electrostatic component of hydration free energy is highly dependent on force field atomic partial charges, influencing a more favorable free energy of hydration in the fixed-charge model compared to the polarizable model.
N-乙酰-β-氨基葡萄糖（NAG）是糖蛋白的重要组成部分，参与许多生物功能。然而，由于实验方法的限制，NAG 分子在最常见的生物环境——水溶液中的构象和动力学性质仍然不清楚。越来越多的人致力于使用分子动力学模拟在原子水平上探测 NAG 及含 NAG 的大分子（如肽聚糖和聚合几丁质）的结构性质。在这项工作中，我们为 NAG 开发了一个可极化的碳水化合物力场，并使用这个新力场和类似的非极化（固定电荷）模型对比模拟结果的各种性质。我们研究了 NAG 及其低聚物的水溶液；我们探索了构象性质（可旋转键几何形状）、静电性质（偶极矩分布）、动力学性质（自扩散系数）、氢键（水桥结构和动力学）和水合自由能。固定电荷碳水化合物力场表现出与气相中环外羟甲基侧链的相对旋转能和椅/船环扭曲的偏离。可极化力场预测的构象性质与相应的第一性原理结果一致。通过径向分布函数（RDFs）和相关函数研究 NAG-水氢键的模式。发现溶质和溶剂之间的分子间氢键稳定了 NAG 溶液结构，而分子内氢键定义了 NAG 低聚物的糖苷键几何形状。水合自由能的静电分量高度依赖于力场原子部分电荷，与可极化模型相比，固定电荷模型中更有利于水合自由能。
