title: Docking studies on PARP-1 inhibitors: insights into the role of a binding pocket water molecule.
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.
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo 1, 06123 Perugia, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Bellocchi
authors.forename: Antonio
authors.initials: A
authors.lastname: Macchiarulo
authors.forename: Gabriele
authors.initials: G
authors.lastname: Costantino
authors.forename: Roberto
authors.initials: R
authors.lastname: Pellicciari
mesh_terms: D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008958:Models, Molecular; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry; D011487:Protein Conformation; D014867:Water / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014867:Water; D011065:Poly(ADP-ribose) Polymerases