MOLECULAR-DYNAMICS SIMULATION OF GALANIN IN AQUEOUS AND NONAQUEOUS SOLUTION
MOLECULAR-DYNAMICS SIMULATION OF GALANIN IN AQUEOUS AND NONAQUEOUS SOLUTION
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DOI：
10.1021/ja00037a002
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发表时间：
1992-05-20
影响因子：
15
通讯作者：
RIGLER, R
中科院分区：
文献类型：
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作者：
DELOOF, H;NILSSON, L;RIGLER, R
为了增加我们对 29 个残基长的神经肽甘丙肽的了解，进行了计算机模拟。与许多其他小肽的情况一样，甘丙肽在水中几乎没有二级结构，这与在 2,2,2-三氟乙醇中溶剂化时的情况不同。因此，通过对溶剂进行明确处理，对甘丙肽进行周期性边界分子动力学模拟。进行了一项在水中的模拟 (220 ps) 和一项在 2,2,2-三氟乙醇 (120 ps) 中的模拟。在这两种情况下，初始构象都是用 NMR 技术测定的 2,2,2-三氟乙醇中的结构（Wennerberg, A. B. A.；等人 Biochem. Biophys. Res. Commun. 1990, 166, 1102-1109）。在这些不同的环境中观察到非常不同的行为：肽在 2,2,2-三氟乙醇中保持稳定，而在水溶液中 C 端结构域逐渐展开。该肽在 2,2,2-三氟乙醇中的稳定性验证了最初的结构测定。此外，作为对照实验，模拟指出了水分子在促进甘丙肽分子展开方面的独特作用。在这两个模拟中，在螺旋末端发现 i-i + 3 个氢键的概率有所增加。更详细地研究了 H2O 模拟中发生的构象变化，并在展开过程中检测到 3(10) 型螺旋或 i-i + 3 氢键的存在。因此，水分子在展开过程中取代了主链氢键，但这不需要插入“单个”水分子，因为分析表明不同的水分子可以与主链氢键中涉及的原始原子配对。其他观察结果指出了侧链-侧链和侧链-主链相互作用在展开过程中的重要性，赋予每个转变其特定的特征。总之，这些结果表明分子动力学模拟至少可以定性地研究溶剂对肽结构和折叠的影响。
In order to increase our knowledge about the 29-residue-long neuropeptide galanin, computer simulations were carried out. As is the case with many other small peptides, galanin has nearly no secondary structure in water, unlike the situation when solvated in 2,2,2-trifluoroethanol. The galanin peptide was therefore subjected to periodic boundary molecular dynamics simulations with explicit treatment of solvent. One simulation in water (220 ps) and one simulation in 2,2,2-trifluoroethanol (120 ps) were carried out. In both cases the initial conformation was the structure, in 2,2,2-trifluoroethanol, as determined with NMR techniques (Wennerberg, A. B. A.; et al. Biochem. Biophys. Res. Commun. 1990, 166, 1102-1109). A very different behavior was observed in these different environments: the peptide remained stable in 2,2,2-trifluoroethanol while in the aqueous solution progressive unfolding of the C-terminal domain took place. The stability of the peptide in 2,2,2-trifluoroethanol validates the original structure determination. In addition, as a control experiment, the simulation points to the unique role of the water molecules in promoting the unfolding of the galanin molecule. In both simulations the probability of finding i-i + 3 hydrogen bonds was increased at the helix termini. The conformational changes occurring in the H2O simulation were studied in more detail, and 3(10)-type helices, or the presence of i-i + 3 hydrogen bonds, were detected during the unfolding. Water molecules thus replace the backbone hydrogen bonds during the unfolding, but this does not require the insertion of a "single" water molecule, as the analysis showed that different water molecules can pair up with the original atoms involved in the backbone hydrogen bond. Other observations point to the importance of side chain-side chain and side chain-main chain interactions during the unfolding process, giving each transition its specific characteristics. In conclusion these results show that molecular dynamics simulations allow, at least qualitatively, the study of solvent effects on peptide structure and folding.