A MODEL OF THE MOLTEN GLOBULE STATE FROM MOLECULAR-DYNAMICS SIMULATIONS
A MODEL OF THE MOLTEN GLOBULE STATE FROM MOLECULAR-DYNAMICS SIMULATIONS
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DOI：
10.1073/pnas.89.11.5142
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发表时间：
1992-06-01
影响因子：
11.1
通讯作者：
LEVITT, M
中科院分区：
文献类型：
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作者：
DAGGETT, V;LEVITT, M
人们普遍认为蛋白质的一级序列决定了它的三维结构。然而，要获得有关实际蛋白质折叠过程和中间状态的详细结构信息已被证明是困难的。我们提出了分子动力学模拟的结果展开还原牛胰蛋白酶抑制剂。所得到的部分“变性”状态相对于原始状态（11- 25%）是致密的，但膨胀的；膨胀不是由水分子的涌入引起的。这些结构是可移动的，总的二级结构含量与天然蛋白相当。蛋白质经历了相对局部的展开，最大的结构变化发生在环区。尽管侧链的包装受到损害，但疏水核心仍保持不变。在模拟中显示的性质与展开到熔融球态是一致的。我们的模拟提供了对这种状态和水-蛋白质相互作用细节的深入观察，这些还不能通过实验获得。
It is generally accepted that a protein's primary sequence determines its three-dimensional structure. It has proved difficult, however, to obtain detailed structural information about the actual protein folding process and intermediate states. We present the results of molecular dynamics simulations of the unfolding of reduced bovine pancreatic trypsin inhibitor. The resulting partially "denatured" state was compact but expanded relative to the native state (11-25 %); the expansion was not caused by an influx of water molecules. The structures were mobile, with overall secondary structure contents comparable to those of the native protein. The protein experienced relatively local unfolding, with the largest changes in the structure occurring in the loop regions. A hydrophobic core was maintained although packing of the side chains was compromised. The properties displayed in the simulation are consistent with unfolding to a molten globule state. Our simulations provide an in-depth view of this state and details of water-protein interactions that cannot yet be obtained experimentally.