Molecular dynamics simulation of HIV-1 protease in a crystalline environment and in solution.
Molecular dynamics simulation of HIV-1 protease in a crystalline environment and in solution.
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DOI：
10.1021/bi00057a007
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发表时间：
1993-02
期刊：
影响因子：
2.9
通讯作者：
D. York;T. Darden;L. Pedersen;M. Anderson
中科院分区：
文献类型：
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作者：
D. York;T. Darden;L. Pedersen;M. Anderson
模拟的未结合形式的人类免疫缺陷病毒1型蛋白酶已进行到200 ps的结晶环境中，并在溶液中。溶液模拟进行了与和没有电荷平衡抗衡离子。将结果与Wlodawer等人[（1989）Science 245，616]的2.8-A晶体学结构进行了比较，并提出了涉及襟翼区域局部重折叠的溶液结构的建议模型。模拟表明，蛋白酶二聚体的晶体包装环境稳定的皮瓣在一个扩展的构象。二聚体的溶剂化导致瓣片的局部重折叠，瓣片朝向活性位点收缩，从而在尖端形成增加的重叠和更强的亚基间氢键。在溶液中的皮瓣重叠的程度被观察到取决于系统的充电状态。
Simulations of the unbound form of the human immunodeficiency virus type 1 protease have been carried out to 200 ps in a crystalline environment and in solution. Solution simulations were performed with and without charge-balancing counterions. The results are compared with the 2.8-A crystallographic structure of Wlodawer et al. [(1989) Science 245, 616], and a proposed model for the solution structure which involves local refolding of the flap regions is presented. The simulations suggest the crystal packing environment of the protease dimer stabilizes the flaps in an extended conformation. Solvation of the dimer leads to local refolding of the flaps which contract toward the active site, forming increased overlap and stronger intersubunit hydrogn bonding at the tips. The degree to which the flaps overlap in solution is observed to depend on the charge state of the system.