Meredith Reagan J, Zhang Wenhui, Yoon Mi-Kyung, Hu Xiaosong, Carmichael Ian, Serianni Anthony S
Department of Chemistry and Biochemistry, University of Notre Dame Notre Dame IN 46556 USA
Texas Biomedical Research Institute San Antonio TX 78227 USA.
RSC Adv. 2024 Sep 23;14(41):30286-30294. doi: 10.1039/d4ra06062h. eCollection 2024 Sep 18.
analysis (Meredith , 2022, , 3135-3141) is a new NMR-based method to treat ensembles of redundant NMR spin-coupling constants (-couplings) to obtain experiment-based probability distributions of molecular torsion angles in solution. Work reported to date on modeling the conformations of -glycosidic linkages of oligosaccharides using three conventional -coupling constraints ( , , ) has shown that the method gives mean torsion angles and circular standard deviations (CSDs) for in very good agreement with those obtained by MD simulation. On the other hand, CSDs for determined by analysis have consistently been much larger than those determined by MD, calling into question either the reliability of analysis or MD to accurately predict this behavior. Prior work has shown that this discrepancy does not stem from the limitations of DFT-based -coupling equation parameterization where secondary conformational dependencies can introduce uncertainties. The present work re-visits this problem by incorporating a new nonconventional -coupling constraint into analyses of , namely, a geminal (two-bond) -value that exhibits a strong primary dependence on . The latter property pertains explicitly to linkages contributed by GlcNAc pyranosyl rings and pyranosyl rings devoid of substituents at C2 (, deoxy residues) where known secondary contributions to magnitude caused by C-O bond rotation involving the coupled carbon are negligible or absent. The results show that when values are added to the analysis, CSDs reduce considerably, bringing them into better alignment with those obtained by MD simulation. The cause of the discrepancy when only three conventional -couplings are used to treat appears to be associated with the two-bond , which has properties that make it less effective than the non-conventional as a discriminator of different conformational models of .
分析（梅雷迪思，2022年，第3135 - 3141页）是一种基于核磁共振的新方法，用于处理冗余核磁共振自旋耦合常数（耦合）的集合，以获得溶液中分子扭转角的基于实验的概率分布。迄今为止，使用三种传统耦合约束（、、）对寡糖的糖苷键构象进行建模的工作表明，该方法给出的扭转角平均值和圆形标准偏差（CSD）与通过分子动力学模拟获得的结果非常吻合。另一方面，通过分析确定的CSD一直比通过分子动力学确定的要大得多，这让人质疑分析或分子动力学准确预测这种行为的可靠性。先前的工作表明，这种差异并非源于基于密度泛函理论的耦合方程参数化的局限性，在这种参数化中，二级构象依赖性可能会引入不确定性。本工作通过在对的分析中纳入一种新的非常规耦合约束，即对具有强烈一级依赖性的偕偶（双键）值，重新审视了这个问题。后一种性质明确适用于由GlcNAc吡喃糖环和在C2处没有取代基的吡喃糖环（，脱氧残基）贡献的键，在这些键中，涉及耦合碳的C - O键旋转对大小的已知二级贡献可以忽略不计或不存在。结果表明，当将值添加到分析中时，CSD会大幅降低，使其与通过分子动力学模拟获得的结果更趋于一致。当仅使用三种传统耦合来处理时出现差异的原因似乎与双键有关，其性质使其作为不同构象模型的区分器不如非常规有效。
