Practical database screening with docking tools.

As an increasing number of pharmaceutically relevant target 3D structures is becoming available, efficient techniques for exploiting the information contained in these structures gain importance over massive experimental screening (Bailey and Brown 2001). One of these techniques is virtual screening through docking calculations, i.e., the search for those compounds in a database of small organic compounds that display favorable steric as well as electrostatic interactions to the target binding site (Walters et al. 1998; Stahl 2000; Good 2001). Docking programs consist of two essential parts: an algorithm that searches the conformational, rotational, and translational space available to a candidate molecule within the binding site, and an objective function that is to be minimized during this process: a crude measure of binding affinity or receptor-ligand complementarity usually referred to as a scoring function. In order to be successful as a virtual screening tool, a docking program must be able to find optimum docking solutions for active molecules in accordance with experiment, it should be able to separate active compounds from inactive ones, and it should use no more than 2–3 min of CPU time per compound to be applicable to large libraries.