PROTEIN UNFOLDING PATHWAYS EXPLORED THROUGH MOLECULAR-DYNAMICS SIMULATIONS
PROTEIN UNFOLDING PATHWAYS EXPLORED THROUGH MOLECULAR-DYNAMICS SIMULATIONS
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DOI：
10.1006/jmbi.1993.1414
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发表时间：
1993-07-20
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
在这里，我们描述的牛胰蛋白酶抑制剂（BPTI）在溶液中的分子动力学模拟的结果在各种温度下，有和没有二硫键。蛋白质的还原形式在高温下展开为具有熔融球状态的所有性质的构象集合。在这个帐户中，我们概述了天然和熔融球状态之间的实际展开过程的结构细节。解折叠的第一步涉及蛋白质的膨胀，这破坏了包装相互作用。溶剂可接近的表面积也迅速增加。解折叠主要定位于分子的转角和环区域，同时保持二级结构完整。然后，有更多的二级结构和非母语的话轮逐渐展开变得普遍。这种相同的轨迹继续下去，发生了更剧烈的展开，导致了一种相对紧凑的状态，缺乏稳定的二级结构。
Herein we describe the results of molecular dynamics simulations of the bovine pancreatic trypsin inhibitor (BPTI) in solution at a variety of temperatures both with and without disulfide bonds. The reduced form of the protein unfolded at high temperature to an ensemble of conformations with all the properties of the molten globule state. In this account we outline the structural details of the actual unfolding process between the native and molten globule states. The first steps of unfolding involved expansion of the protein, which disrupted packing interactions. The solvent-accessible surface area also quickly increased. The unfolding was localized mostly to the turn and loop regions of the molecule, while leaving the secondary structure intact. Then, there was more gradual unfolding of the secondary structure and non-native turns became prevalent. This same trajectory was continued and more drastic unfolding occurred that resulted in a relatively compact state devoid of stable secondary structure.