Marrone T J, Resat H, Hodge C N, Chang C H, McCammon J A
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla 92093-0365, USA.
Protein Sci. 1998 Mar;7(3):573-9. doi: 10.1002/pro.5560070305.
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.
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。
