Virtual Screening of Large Databases of Small-Molecule Drugs

Nouri Neamati is an associate professor in the USC School of Pharmacy?s Department of Pharmacology and Pharmaceutical Sciences. His research interests include drug design and discovery, database mining of small-molecule compounds, molecular pharmacology, and chemoinformatics.

Neamati has established an internationally recognized program in drug design and discovery with a major focus on antiviral and anticancer therapeutics. He and his research team use computational chemistry to match chemical compounds to biological processes in order to design drugs for the treatment of various diseases, including cancer and HIV/AIDS. Using the structural information available for many existing drugs and targets, Neamati and his team develop small-molecule compounds based on known drugs and the size and shape of a targeted cavity within a protein of a diseased cell. The compound must conform closely to the shape of the cavity in order to bind to it and inhibit the function of the protein.

Neamati's team uses HPCC resources to test thousands of compounds against the shape of single, diseased cells to determine the best fit. His team has developed a database, containing 10 million small-molecule compounds, that is readily searchable using two-dimensional fingerprinting algorithms. The team has also calculated up to 200 conformations for each compound to generate approximately 2 billion structures that are fully searchable in three dimensions.

Neamati and his team are currently testing numerous compounds that could lead to major breakthroughs in the treatment of cancer and HIV/AIDS.

Neamati's research is funded by the National Institutes of Health (NIH), Department of Defense, American Lung Association, American Association for Cancer Research, and the Susan G. Komen Breast Cancer Foundation. He has been awarded the NIH Technology Transfer Award, the Stop Cancer Award, the GlaxoSmithKline Drug Discovery and Development Award, and an Idea Award from the Department of Defense's Congressionally Directed Ovarian and Breast Cancer Research Program.