与HIV蛋白酶结合的DMP323和A76928的溶剂化研究：使用巨正则蒙特卡罗模拟分析水合位点
Solvation studies of DMP323 and A76928 bound to HIV protease: analysis of water sites using grand canonical Monte Carlo simulations.
作者信息
Marrone T J, Resat H, Hodge C N, Chang C H, McCammon J A
机构信息
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla 92093-0365, USA.
出版信息
Protein Sci. 1998 Mar;7(3):573-9. doi: 10.1002/pro.5560070305.
Abstract
We examine the water solvation of the complex of the inhibitors DMP323 and A76928 bound to HIV-1 protease through grand canonical Monte Carlo simulations, and demonstrate the ability of this method to reproduce crystal waters and effectively predict water positions not seen in the DMP323 or A76928 structures. The simulation method is useful for identifying structurally important waters that may not be resolved in the crystal structures. It can also be used to identify water positions around a putative drug candidate docked into a binding pocket. Knowledge of these water positions may be useful in designing drugs to utilize them as bridging groups or displace them in the binding pocket. In addition, the method should be useful in finding water sites in homology models of enzymes for which crystal structures are unavailable.
摘要
我们通过巨正则蒙特卡罗模拟研究了与HIV-1蛋白酶结合的抑制剂DMP323和A76928复合物的水合作用，并证明了该方法再现晶体水以及有效预测在DMP323或A76928结构中未出现的水位置的能力。该模拟方法有助于识别在晶体结构中可能未解析的结构重要水。它还可用于识别对接至结合口袋中的假定药物候选物周围的水位置。了解这些水位置可能有助于设计药物，将它们用作桥连基团或在结合口袋中取代它们。此外，该方法在寻找晶体结构不可用的酶的同源模型中的水位点方面应该是有用的。
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本文引用的文献
1
Molecular basis of HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with cyclic urea inhibitors.HIV-1蛋白酶耐药性的分子基础：与环脲抑制剂复合的突变蛋白酶的结构分析
Biochemistry. 1997 Feb 18;36(7):1573-80. doi: 10.1021/bi962234u.
2
Enzyme-inhibitor association thermodynamics: explicit and continuum solvent studies.酶-抑制剂结合热力学：显式溶剂与连续介质溶剂研究
Biophys J. 1997 Feb;72(2 Pt 1):522-32. doi: 10.1016/s0006-3495(97)78692-2.
3
Grand canonical ensemble Monte Carlo simulation of the dCpG/proflavine crystal hydrate.dCpG/硫酸原黄素晶体水合物的巨正则系综蒙特卡罗模拟
Biophys J. 1996 Sep;71(3):1179-90. doi: 10.1016/S0006-3495(96)79322-0.
4
Mapping hydration water molecules in the HIV-1 protease/DMP323 complex in solution by NMR spectroscopy.通过核磁共振光谱法对溶液中HIV-1蛋白酶/DMP323复合物中的水化水分子进行映射。
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5
Solution NMR evidence that the HIV-1 protease catalytic aspartyl groups have different ionization states in the complex formed with the asymmetric drug KNI-272.溶液核磁共振证据表明，在与不对称药物KNI-272形成的复合物中，HIV-1蛋白酶催化天冬氨酰基团具有不同的电离状态。
Biochemistry. 1996 Aug 6;35(31):9945-50. doi: 10.1021/bi961268z.
6
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