Prediction of protein-ligand interactions. Docking and scoring: successes and gaps.

Computational methods have become standard in today’s medicinal chemistry tool kit. Like any tool, it is important to periodically evaluate utility and ask how function can be improved. In this section of the Journal, we call attention to the area of calculating molecular interactions, specifically docking, the positioning of a ligand in a protein binding site, and scoring, the quality assessment of docked ligands. As several recent reviews have made clear, 1-3 the technology has been productive for both finding and elaborating bioactive molecules. But has docking and scoring delivered on the promises first made over 20 years ago? To consider that question, we follow up on an extensive symposium held in Philadelphia during the 2004 Fall National Meeting of the American Chemistry Society and on subsequent meetings sponsored by the National Institutes of Health (NIH) and the National Institute of Standards and Technology (NIST) in 2005 and 2006 to address the outcomes of the American Chemical Society symposium. Speakers at the symposium were invited to contribute original manuscripts to be published with this overview to highlight the area of docking and scoring and to identify some of the major gaps yet to be addressed. 4-10