Combined Molecular Dynamics Simulations and Experimental Studies of the Structure and Dynamics of Poly-Amido-Saccharides
Combined Molecular Dynamics Simulations and Experimental Studies of the Structure and Dynamics of Poly-Amido-Saccharides
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DOI：
10.1021/jacs.6b01837
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发表时间：
2016-05-25
影响因子：
15
通讯作者：
Grinstaff, Mark W.
中科院分区：
文献类型：
--
作者：
Chin, Stacy L.;Lu, Qing;Grinstaff, Mark W.
聚酰胺糖(PAS)是一种以碳水化合物为基础的对映体合成聚合物，其中的糖重复单元通过酰胺键连接。这种独特且相对刚性的吡喃糖主链有助于它们明确的螺旋二级结构和显着的化学性质。合成了葡萄糖(GLC-)和半乳糖(GAL-)PAS10-聚体结构，并用分子动力学(MD)模拟和实验测量对其进行了研究。量子力学DFT能量最小化计算，以及包括圆二向色性、(HC)-H-1-C-13-HSQC和H-1，H-1-NOESY 2D-核磁共振研究在内的实验观测数据，验证了使用改进的CHARMM力场产生的全原子模拟模型。水的径向分布函数在GLC-和GAL-PAS体系中表现出明显的差异，这与观察到的GAL-PASS和GLC-PAS之间的溶解度差异有很好的相关性。计算分析和分子动力学模拟结果与实验结果吻合较好，验证了所提出的模型是新型GLC-PASS和GAL-PASS的可靠表示。
Poly-amido-saccharides (PAS) are carbohydrate-based, enantiopure synthetic polymers in which sugar repeat units are joined by amide linkages. This unique and relatively rigid pyranose backbone contributes to their defined helical secondary structure and remarkable chemical properties. Glucose- (glc-) and galactose- (gal-) PAS 10-mer structures are synthesized and investigated with molecular dynamics (MD) simulations and experimental measurements. Quantum mechanical DFT energy minimization calculations, as well as experimental observables including circular dichroism, (HC)-H-1-C-13-HSQC, and H-1,H-1-NOESY 2D-NMR studies, validated the all-atom simulation models produced using a modified CHARMM force field. Water radial distribution functions show distinct differences in the glc- and gal-PAS systems that correlate well with observed differences in solubility between gal-PASs and glc-PASs. The computational analysis and MD simulations are in good agreement with experimental results, validating the proposed models as reliable representations of novel glc- and gal-PASs.