Atomistic simulation study of the coupled motion of amino acid residues and water molecules around protein HP-36: Fluctuations at and around the active sites
Atomistic simulation study of the coupled motion of amino acid residues and water molecules around protein HP-36: Fluctuations at and around the active sites
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DOI：
10.1021/jp048532f
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发表时间：
2004-08-19
影响因子：
3.3
通讯作者：
Bagchi, B
中科院分区：
文献类型：
--
作者：
Bandyopadhyay, S;Chakraborty, S;Bagchi, B
鸡绒毛头子结构域通常称为 HP-36，是一种肌动蛋白结合蛋白。它由三个 α 螺旋和四个螺旋中的 36 个氨基酸残基组成。研究发现该蛋白质的生物活性集中在含有 10 个氨基酸残基的 helix-3 周围。我们用明确的水对 HP-36 进行了原子分子动力学模拟，以研究氨基酸残基的动力学、周围水分子的动力学和蛋白质的生物活性之间的相关性（如果有的话）。我们计算了单个氨基酸残基的均方根偏差（RMSD）的时间轨迹、水分子的旋转和平移运动，以及HP-36不同片段附近的蛋白质残基和界面水分子之间形成的氢键的动力学。我们发现短螺旋 1 和 2 中的氨基酸残基没有表现出有趣的动力学；他们的 RMSD 的时间轨迹仅显示出随时间的微小变化。相比之下，helix-3（具有生物活性的残基）中的残基表现出非常有趣的动力学，通常表现出大幅度的运动，有时几乎是振荡运动。同时，helix-3 附近的水分子被发现表现出明显更快的旋转和平移运动。据观察，helix-3 中的残基与界面水分子之间形成的氢键的结构弛豫比其他两个螺旋的氢键的结构弛豫更快。根据径向分布函数对蛋白质周围水分子的结构排列进行分析表明，螺旋 3 周围的水分子不仅较少，而且结构也比螺旋 1 和 2 周围的水分子要少。这有点令人惊讶，因为第三个螺旋含有多个亲水基团。对蛋白质结构的分析表明，蛋白质核心内几乎没有极性亲水残基，这部分解释了helix-3周围缺乏水分子结构。
The chicken villin headpiece subdomain, popularly known as HP-36, is an actin binding protein. It consists of 36 amino acid residues in three alpha-helices and four coils. The biological activity of the protein is found to be centered around helix-3, which contains 10 amino acid residues. We have performed atomistic molecular dynamics simulations of HP-36 with explicit water in order to investigate the correlation, if any, between the dynamics of the amino acid residues, dynamics of surrounding water molecules, and the biological activity of the protein. We calculate the time trajectory of the root mean square deviation (RMSD) of individual amino acid residues, the rotational and translational motion of water molecules, and the dynamics of hydrogen bonds formed between the protein residues and the interfacial water molecules near different segments of HP-36. We find that the amino acid residues in the short helices 1 and 2 exhibit no interesting dynamics; the time trajectory of their RMSD shows only minor changes with time. In contrast, the residues in helix-3 (the biologically active one) show highly interesting dynamics, often exhibiting large amplitude, sometimes nearly oscillatory motions. Simultaneously, the water molecules near helix-3 are found to exhibit noticeably faster rotational and translational motions. It has been observed that the structural relaxation of the hydrogen bonds formed between the residues in helix-3 and the interfacial water molecules is faster than that for the other two helices. Analysis of the structural arrangement of water molecules around the protein in terms of the radial distribution function shows that not only are there fewer water molecules around helix-3 but they are also less structured than those around helices 1 and 2. This is somewhat surprising because the third helix contains several hydrophilic groups. Analysis of the structure of the protein shows that few polar hydrophilic residues remain buried within the core of the protein, which partly explains the lack of structure of water molecules around helix-3.