Docking studies on PARP-1 inhibitors: insights into the role of a binding pocket water molecule

The binding mode of a series of competitive PARP-1 inhibitors was investigated employing a molecular docking approach by using Autodock 3.0. A particular attention was given to the role played by a water molecule present in some but not all the so far available crystal structures of the catalytic domain of PARP-1. Good correlation between calculated binding energies and experimental inhibitory activities was obtained either by including (r(2) = 0.87) or not (r(2) = 0.84) the structural water molecule. Closer inspection of our results suggested that this water molecule should be considered part of the hydration shell of polar inhibitors and not as a structural water. (C) 2004 Elsevier Ltd. All rights reserved.