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

Bioorg Med Chem. 2005 Feb 15;13(4):1151-7. doi: 10.1016/j.bmc.2004.11.024.

Abstract

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 (r2=0.87) or not (r2=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.

MeSH terms

  • Catalytic Domain
  • Enzyme Inhibitors / pharmacology*
  • Models, Molecular
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Poly(ADP-ribose) Polymerases / chemistry
  • Protein Conformation
  • Water / chemistry*

Substances

  • Enzyme Inhibitors
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Water
  • Poly(ADP-ribose) Polymerases