Exploiting ordered waters in molecular docking.
A current weakness in docking is the treatment of water-mediated protein-ligand interactions. We explore switching ordered water molecules "on" and "off" during docking screens of a large library. The method assumes additivity and scales linearly with the number of waters sampled despite the exponential growth in configurations. It is tested for ligand enrichment against 24 targets, exploring up to 256 water configurations. Water inclusion increased enrichment substantially for 12 targets, while most others were largely unaffected.
Huang
Niu
N
Department of Pharmaceutical Chemistry, University of California-San Francisco, 1700 Fourth Street, San Francisco, California 94158-2550, USA.
Shoichet
Brian K
BK
D001665:Binding Sites; D003198:Computer Simulation; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D014867:Water / Q000737:chemistry*
D008024:Ligands; D014867:Water