MOLECULAR-DYNAMICS SIMULATIONS OF HELIX DENATURATION
MOLECULAR-DYNAMICS SIMULATIONS OF HELIX DENATURATION
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DOI：
10.1016/0022-2836(92)90264-k
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发表时间：
1992-02-20
影响因子：
5.6
通讯作者：
LEVITT, M
中科院分区：
文献类型：
--
作者：
DAGGETT, V;LEVITT, M
了解α-螺旋经历的结构转变将有助于阐明蛋白质中的这种运动及其在蛋白质折叠中的作用。我们给出了分子动力学模拟的结果，以研究在真空和溶剂存在下短的聚丙氨酸多肽(13个残基)中的这些转变。在真空中，螺旋状态在所有温度下都占主导地位，而在溶液中，螺旋状态随着温度的升高而融化。在溶液中的低温下，多肽主要是螺旋的，而在中等温度下，多肽大部分时间在具有中等螺旋的不同构象之间波动，例如不完全螺旋或完全非螺旋。这些构象中有许多是由带有中间非螺旋残基的短螺旋片段组成的。在高温下，多肽展开，并呈现各种塌陷的非结构状态。在高温下断裂的螺旋内氢键没有被部分展开形式的多肽中的水分子的氢键完全补偿。温度的升高破坏了螺旋结构和肽与水的相互作用。水在促进折叠方面发挥了主要但间接的作用，而不是专门竞争肽内的氢键。讨论了我们的结果对蛋白质折叠的影响。
An understanding of the structural transitions that an α-helix undergoes will help to elucidate such motions in proteins and their role in protein folding. We present the results of molecular dynamics simulations to investigate these transitions in a short polyalanine peptide (13 residues) bothin vacuoand in the presence of solvent. The denaturation of this peptide was monitored as a function of temperature (ranging from 5 to 200 °C).In vacuo, the helical state predominated at all temperatures, whereas in solution the helix melted with increasing temperature. The peptide was predominantly helical at low temperature in solution, while at intermediate temperatures the peptide spent the bulk of the time fluctuating between different conformations with intermediate amounts of helix, e.g. not completely helical nor entirely non-helical. Many of these conformations consisted of short helical segments with intervening non-helical residues. At high temperature the peptide unfolded and adopted various collapsed unstructured states. The intrahelical hydrogen bonds that break at high temperature were not fully compensated by hydrogen bonds with water molecules in the partially unfolded forms of the peptide. Increases in temperature disrupted both the helical structure and the peptide-water interactions. Water played a major but indirect role in facilitating unfolding, as opposed to specifically competing for the intrapeptide hydrogen bonds. The implications of our results to protein folding are discussed.