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首页> 外文期刊>The journal of physical chemistry, A. Molecules, spectroscopy, kinetics, environment, & general theory >Quantifying the Role of Water in Protein-Carbohydrate Interactions
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Quantifying the Role of Water in Protein-Carbohydrate Interactions

机译：定量水在蛋白质-碳水化合物相互作用中的作用

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摘要

Water-mediated interactions play a key role in carbohydrate-lectin binding, where the interactions involve a conserved water that is separated from the bulk solvent and present a bridge between the side chains of the protein and the carbohydrate ligand. To apply quantum mechanical methods to examine the role of conserved waters, we present an analysis in which the relevant carbohydrate atoms are modeled by methanol, and in which the protein is replaced by a limited number of amino acid side chains. Clusters containing a conserved water and a representative amino acid fragment were also examined to determine the influence of amino acid side chains on interaction energies. To quantify the differential binding energies of methanol versus water, quantum mechanical calculations were performed at the B3LYP/6-311++G(3df, 3pd)//B3LYP/6-31+G(d) level in which either a methanol molecule was bound to the conserved water (liganded state) or in which a water molecule replaces the methanol (unliganded state). Not surprisingly, the binding of a water to clusters containing charged amino acid side chains was more favorable by 1.55 to 7.23 kcal/mol than that for the binding of a water to the corresponding pure water clusters. In contrast, the binding energy of water to clusters containing polar-uncharged amino acid side chains ranged from 4.35 kcal/mol less favorable to 4.72 kcal/mol more favorable than for binding to the analogous pure water clusters. The overall trend for the binding of methanol versus water, in any of the clusters, favored methanol by an average value of 1.05 kcal/mol. To extend these studies to a complex between a protein (Concanavalin A) and its carbohydrate ligand, a cluster was examined that contained the side chains of three key amino acids, namely asparagine, aspartate, and arginine, as well as a key water molecule, arranged as in the X-ray diffraction structure of Con A. Again, using methanol as a model for the endogenous carbohydrate ligand, energies of -5.94 kcal/mol and -5.70 kcal/mol were obtained for the binding of methanol and water, respectively, to the Con A-water cluster. The extent to which cooperativity enhanced the binding energies has been quantified in terms of nonadditive three body contributions. In general, the binding of water of methanol to neutral dimers formed cooperative clusters; in contrast, the cooperativity in charged clusters depended on the overall geometry as well as the charge.
机译：水介导的相互作用在碳水化合物-凝集素结合中起关键作用，其中相互作用涉及与主体溶剂分离的保守水，并在蛋白质和碳水化合物配体的侧链之间架起桥梁。为了应用量子力学方法检查保守水的作用，我们提出了一种分析，其中相关的碳水化合物原子由甲醇模拟，并且其中的蛋白质被有限数量的氨基酸侧链取代。还检查了含有保守水和代表性氨基酸片段的簇，以确定氨基酸侧链对相互作用能的影响。为了量化甲醇与水的差分结合能，在其中一个甲醇分子处于B3LYP / 6-311 ++ G（3df，3pd）// B3LYP / 6-31 + G（d）水平上进行了量子力学计算与保守水结合（结合态），或水分子代替甲醇（结合态）。毫不奇怪，与将水与相应的纯水簇结合相比，将水与包含带电荷的氨基酸侧链的簇的结合更有利地为1.55至7.23kcal / mol。相反，水与含有极性不带电荷的氨基酸侧链的簇的结合能比与结合至类似的纯水簇相比，在较不有利的4.35kcal / mol的范围内，对更有利于4.72kcal / mol的范围。在任何簇中，甲醇与水结合的总体趋势均以1.05 kcal / mol的平均值偏向于甲醇。为了将这些研究扩展到蛋白质（伴刀豆球蛋白A）与其碳水化合物配体之间的复合物，我们研究了一个簇，该簇包含三个关键氨基酸的侧链，即天冬酰胺，天冬氨酸和精氨酸，以及一个关键水分子，再次按照甲醇A的X射线衍射结构排列。再次，使用甲醇作为内源碳水化合物配体的模型，分别获得了-5.94 kcal / mol和-5.70 kcal / mol的能量，用于结合甲醇和水，到Con A-water集群。协同作用增强结合能的程度已通过非累加的三体贡献进行了定量。通常，甲醇中的水与中性二聚体的结合形成协作簇。相反，带电簇中的协同性取决于整体几何形状以及电荷。

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