BioMaPS Institute and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, United States.
J Am Chem Soc. 2011 Oct 5;133(39):15252-5. doi: 10.1021/ja205251j. Epub 2011 Sep 8.
NMR restrictions are suitable to specify the geometry of a molecule when a single well-defined global free energy minimum exists that is significantly lower than other local minima. Carbohydrates are quite flexible, and therefore, NMR observables do not always correlate with a single conformer but instead with an ensemble of low free energy conformers that can be accessed by thermal fluctuations. In this communication, we describe a novel procedure to identify and weight the contribution to the ensemble of local minima conformers based on comparison to residual dipolar couplings (RDCs) or other NMR observables, such as scalar couplings. A genetic algorithm is implemented to globally minimize the R factor comparing calculated RDCs to experiment. This is done by optimizing the weights of different conformers derived from the exhaustive local minima conformational search program, fast sugar structure prediction software (FSPS). We apply this framework to six human milk sugars, LND-1, LNF-1, LNF-2, LNF-3, LNnT, and LNT, and are able to determine corresponding population weights for the ensemble of conformers. Interestingly, our results indicate that in all cases the RDCs can be well represented by only a few most important conformers. This confirms that several, but not all of the glycosidic linkages in histo-blood group "epitopes" are quite rigid.
NMR 限制条件适用于指定分子的几何形状，当存在单个明确的全局自由能最小值，且其显著低于其他局部最小值时。碳水化合物相当灵活，因此，NMR 可观测值并不总是与单个构象相关，而是与可通过热波动访问的低自由能构象的集合相关。在本通讯中，我们描述了一种新的程序，用于基于与残差偶极耦合（RDC）或其他 NMR 可观测值（如标量耦合）的比较，来识别和加权局部极小构象的集合的贡献。遗传算法被用来通过比较计算的 RDC 与实验来全局最小化 R 因子。这是通过优化来自详尽的局部极小构象搜索程序、快速糖结构预测软件（FSPS）的不同构象的权重来实现的。我们将该框架应用于六种人乳糖，LND-1、LNF-1、LNF-2、LNF-3、LNnT 和 LNT，并能够确定构象集合的相应群体权重。有趣的是，我们的结果表明，在所有情况下，RDC 都可以仅由少数最重要的构象很好地表示。这证实了在组织血型“抗原”中，并非所有的糖苷键，而是有几个糖苷键相当稳定。
