Tj. Marrone et al., SOLVATION STUDIES OF DMP323 AND A76928 BOUND TO HIV PROTEASE - ANALYSIS OF WATER SITES USING GRAND-CANONICAL MONTE-CARLO SIMULATIONS, Protein science, 7(3), 1998, pp. 573-579
We examine the water solvation of the complex of the inhibitors DMP323
and A76928 bound to HIV-1 protease through grand canonical Monte Carl
o simulations, and demonstrate the ability of this method to reproduce
crystal waters and effectively predict water positions not seen in th
e DMP323 or A76928 structures. The simulation method is useful for ide
ntifying structurally important waters that may not be resolved in the
crystal structures. It can also be used to identify water positions a
round a putative drug candidate docked into a binding pocket. Knowledg
e of these water positions may be useful in designing drugs to utilize
them as bridging groups or displace them in the binding pocket. In ad
dition, the method should be useful in finding water sites in homology
models of enzymes for which crystal structures are unavailable.