CRITICAL-EVALUATION OF SEARCH ALGORITHMS FOR AUTOMATED MOLECULAR DOCKING AND DATABASE SCREENING

The DOCK program explores possible orientations of a molecule within a macromolecular active site by superimposing atoms precomputed site po ints. Here we compare a number of different search methods, including an exhaustive matching algorithm based on a single docking graph. We e valuate the performance of each method by screening a small database o f molecules to a variety of macromolecular targets. By varying the amo unt of sampling, we can monitor the time convergence of scores and ran king. We not only show that the site point directed search is tenfold faster than a random search, but that the single graph matching algori thum boosts the speed of database screening up to 60-fold. The new alg orithum, in fact, outperforms the bipartite graph matching algorithum currently used in DOCK. The results indicate that a critical issue for rapid database screening is the extent to which a search method biase s run time toward the highest-ranking molecules. The single docking gr oup matching algorithum will be incorporated into DOCK version 4.0.