A WEB-BASED AUTOMATIC MOLECULAR DOCKING SYSTEM

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Notwithstanding well-known algorithmic weaknesses, molecular docking screens have had important successes in recent years. Like other screening techniques, the goal is to discover novel ligands. False negatives are tolerated, and the emphasis on screening available compounds makes false positives cheap. Docking is now the most practical technique to leverage structure for ligand discovery. Unfortunately, barriers to entry have largely restricted the technique to experts and their collaborators. Docking databases are expensive to acquire, require considerable manipulation, and the software is byzantine. This has diminished the impact of the technique and limited the sorts of problems to which it can be applied. We propose to develop tools and databases that will bring docking to a broad audience, and allow its application to new questions. The first aim is to develop databases and tools that an educated non-expert can use via a web-based application, in the spirit of BLAST. This admittedly goal-oriented aim would provide an enabling technology that would have much impact. The second aim is hypothesis driven: we investigate using docking screening results to fingerprint binding sites for recognition and potentially function.