Critical evaluation of search algorithms for automated molecular docking and database screening

✍ Scribed by Ewing, Todd J. A.; Kuntz, Irwin D.

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 263 KB
• Volume: 18
• Category: Article
• ISSN: 0192-8651
• DOI: 10.1002/(sici)1096-987x(19970715)18:9<1175::aid-jcc6>3.0.co;2-o

✦ Synopsis

The DOCK program explores possible orientations of a molecule within a macromolecular active site by superimposing atoms onto precomputed site points. Here we compare a number of different search methods, including an exhaustive matching algorithm based on a single docking graph. We evaluate the performance of each method by screening a small database of molecules to a variety of macromolecular targets. By varying the amount of sampling, we can monitor the time convergence of scores and rankings. We not only show that the site point᎐directed search is tenfold faster than a random search, but that the single graph matching algorithm boosts the speed of database screening up to 60-fold. The new algorithm, in fact, outperforms the bipartite graph matching algorithm currently used in DOCK. The results indicate that a critical issue for rapid database screening is the extent to which a search method biases run time toward the highest-ranking molecules. The single docking graph matching algorithm will be incorporated into DOCK version 4.0.