High-throughput Direct Structural Screening for Drug Lead Compounds

The Army has an obvious and immediate need for greater exploration of small molecules in the search for novel anti-malarial drugs. The innovative techniques offered in this proposal utilize methods of iterated automated fragment assembly coupled with an intelligent compound screening tool to facilitate scientific advancement. The resulting computational methods can increase the rate and exploration of small molecule space for novel malaria inhibitors. The proposed Phase I research makes use of docking algorithms as prototyping methods for these computational approaches with DHFR as the target of interest. Docking methods will be expanded to include NMR research in Phase II. The Phase I research and development sets the stage for continued Phase II research and development and transition for field use. The technology’s applications go beyond Army needs to all branches of the military, and also commercial and academic drug discovery pipelines. The prospect for commercialization for the resulting technology in the bioinformatics sector is high in light of the increased need for rapid small molecule search strategies.