Stacking and T-shape competition in aromatic-aromatic amino acid interactions
Stacking and T-shape competition in aromatic-aromatic amino acid interactions
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DOI：
10.1021/ja0121639
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发表时间：
2002-05-29
影响因子：
15
通讯作者：
Schettino, V
中科院分区：
文献类型：
--
作者：
Chelli, R;Gervasio, FL;Schettino, V
用分子动力学模拟方法计算了芳香族氨基酸相互作用的平均力势。为了研究苯丙氨酸-苯丙氨酸(Phe-Phe)、苯丙氨酸-酪氨酸(Phe-Tyr)和酪氨酸-酪氨酸(Tyr-Tyr)络合物在真空、水、四氯化碳和甲醇中的堆积和T型竞争，测定了自由能面。除了四氯化碳中的Tyr-Tyr络合物外，堆积结构在所有溶剂中都是最受欢迎的，其中T型结构也很重要。研究了在选定距离处锚定两个α-碳(C-α)的效果。我们发现短的C-α-C-α距离和大的C-α-C-α距离分别有利于堆积和T形结构。我们分析了一组通过实验解析的2396个蛋白质结构。理论自由能与实验模拟的比较表明，Tyr-Tyr相互作用主要发生在蛋白质表面，而Phe-Tyr和Phe-Phe相互作用更频繁地发生在疏水蛋白质核心。对数据库蛋白质结构的Voronoi多面体分析证实了这一点。从自由能计算中发现，蛋白质数据库的分析表明，近端和远端相互作用的芳香族残基分别以堆积和T形为主。
The potential of mean force of interacting aromatic amino acids is calculated using molecular dynamics simulations. The free energy surface is determined in order to study stacking and T-shape competition for phenylalanine-phenylalanine (Phe-Phe), phenylalanine-tyrosine (Phe-Tyr), and tyrosine-tyrosine (Tyr-Tyr) complexes in vacuo, water, carbon tetrachloride, and methanol. Stacked structures are favored in all solvents with the exception of the Tyr-Tyr complex in carbon tetrachloride, where T-shaped structures are also important. The effect of anchoring the two alpha-carbons (C-alpha) at selected distances is investigated. We find that short and large C-alpha-C-alpha distances favor stacked and T-shaped structures, respectively. We analyze a set of 2396 protein structures resolved experimentally. Comparison of theoretical free energies for the complexes to the experimental analogue shows that Tyr-Tyr interaction occurs mainly at the protein surface, while Phe-Tyr and Phe-Phe interactions are more frequent in the hydrophobic protein core. This is confirmed by the Voronoi polyhedron analysis on the database protein structures. As found from the free energy calculation, analysis of the protein database has shown that proximal and distal interacting aromatic residues are predominantly stacked and T-shaped, respectively.