Quantifying the role of water in protein-carbohydrate interactions.
Quantifying the role of water in protein-carbohydrate interactions.
复制标题
量化水在蛋白质-碳水化合物相互作用中的作用。
DOI：
10.1021/jp035027u
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Woods,RobertJ
中科院分区：
文献类型：
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作者：
Tschampel,SarahM;Woods,RobertJ
水介导的相互作用在碳水化合物-凝集素结合中起着关键作用，其中相互作用涉及从本体溶剂中分离的保守水，并在蛋白质侧链和碳水化合物配体之间提供桥梁。为了应用量子力学方法来研究保守的沃茨的作用，我们提出了一个分析，其中相关的碳水化合物原子建模的甲醇，并在其中的蛋白质被替换为有限数量的氨基酸侧链。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B3 LYP/6-311++G（3df，3 pd）//B3 LYP/6-31+G（d）水平下进行量子力学计算，其中甲醇分子与保守的水结合（配体状态）或其中水分子取代甲醇（非配体状态）。毫不奇怪，水与含有带电氨基酸侧链的簇的结合比水与相应的纯水簇的结合更有利1.55至7.23 kcal/mol。与此相反，水的结合能的集群含有极性不带电的氨基酸侧链的范围从4.35千卡/摩尔不太有利的4.72千卡/摩尔更有利的比结合到类似的纯水集群。在任何簇中，甲醇与水结合的总体趋势有利于甲醇，平均值为1.05 kcal/mol。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，研究了一个簇，该簇包含三个关键氨基酸（即天冬酰胺、天冬氨酸和精氨酸）的侧链以及一个关键水分子，其排列方式与Con A的X射线衍射结构相同。同样，使用甲醇作为内源性碳水化合物配体的模型，甲醇和水分别与Con A−水簇结合的能量为−5.94 kcal/mol和−5.70 kcal/mol。在何种程度上协同增强的结合能已被量化的非加性三体贡献。在一般情况下，结合水或甲醇的中性二聚体形成合作集群，相反，在带电集群的协同性取决于整体的几何形状以及电荷。
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 or methanol to neutral dimers formed cooperative clusters; in contrast, the cooperativity in charged clusters depended on the overall geometry as well as the charge.