Theoretical Investigations on the Conformation of the β-D-Arabinofuranoside Ring
Theoretical Investigations on the Conformation of the β-D-Arabinofuranoside Ring
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DOI：
10.1021/ct100450s
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发表时间：
2011-02-01
影响因子：
5.5
通讯作者：
Lowary, Todd L.
中科院分区：
文献类型：
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作者：
Taha, Hashem A.;Roy, Pierre-Nicholas;Lowary, Todd L.
研究了一种用于呋喃糖环构象分析的方法，该方法包括预测（3）J（H，H），其可以直接与实验值进行比较。该方法不同于传统的用于呋喃糖环构象研究的PSEUROT方法，其先前被应用于许多α-D-阿拉伯呋喃糖苷，并且使得能够将（3）J（H，H）值与从NMR光谱获得的值进行直接比较。在本文中，使用这种方法来研究含有β-连接的阿拉伯呋喃糖残基的寡糖的构象偏好的报告。进行密度泛函理论（DFT）计算，以获得专门为这些环系统量身定制的Karplus关系。此外，从GLYCAM/AMBER分子动力学模拟获得的概率分布被用于从这些Karplus关系计算（3）J（H，H）值。然而，与α-阿拉伯呋喃糖苷获得的结果不同，β-阿拉伯呋喃糖苷计算的（3）J（H，H）值与实验值的一致性较差。这促使其他方法的探索，包括重新评估和优化的初始MD协议，使用各种力场模型，并重新计算DFT衍生的耦合配置文件使用优化的基组。经过广泛的研究，我们建立了从MD模拟获得的构象分布与GLYCAM力场和呋喃糖苷特异性CHARMM力场结合DFT Karplus方程，使用增强基组（B3 LYP/aug-cc-pVTZ-J）确定，与实验（3）J（H，H）值相比，产生了最佳的一致性。使用这些方案，除了（3）J（2，3）和（3）J（3，4）被低估外，所有偶联途径在（3）J（H，H）中存在相对良好的一致性。
A method for the conformational analysis of furanose rings that involves the prediction of (3)J(H,H) that can be compared directly to experimental values is investigated. This method, which differs from the traditional PSEUROT approach for conformational studies of furanose rings, was previously applied to a number of alpha-D-arabinofuranosides and enabled the direct comparison of (3)J(H,H) values to those obtained from NMR spectroscopy. In this paper, the use of this approach to study the conformational preferences of oligosaccharides containing beta-linked arabinofuranose residues is reported. Density functional theory (DFT) calculations were carried out to derive Karplus relationships that are specifically tailored for these ring systems. In addition, probability distributions obtained from GLYCAM/AMBER molecular dynamics simulations were employed to calculate (3)J(H,H) values from these Karplus relationships. However, unlike the results obtained with alpha-arabinofuranosides, the (3)J(H,H) values computed for beta-arabinofuranosides agreed poorly with experimental values. This prompted the exploration of other methodologies including reevaluation and optimization of the initial MD protocol, use of various force field models, and recalculation of the DFT-derived coupling profiles using an optimized basis set. After extensive investigations, we established that the conformer distributions obtained from MD simulations with the GLYCAM force fields and the furanoside-specific CHARMM force field in combination with the DFT Karplus equations, determined using an augmented basis set (B3LYP/aug-cc-pVTZ-J), produced the best agreement compared to experimental (3)J(H,H) values. Using these protocols, there is relatively good agreement in (3)J(H,H) for all coupling pathways with the exception of (3)J(2,3) and (3)J(3,4), which are underestimated.