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| Sripriya Chellappan and Michael K. Gilson. Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, MD 20850 |
| The emergence of HIV strains that are resistant to current protease inhibitors has challenged the effectiveness of these inhibitors in the treatment of AIDS. There is thus a need for new protease inhibitors that effectively inhibit both the wild type and its mutant forms. We aim to accelerate the discovery of such compounds by designing targeted combinatorial libraries, using computational docking and the substrate envelope concept as criteria for affinity and broad specificity. The design protocol is optimized through systematic studies of factorization of the combinatorics, and through the use of a genetic algorithm for automated ligand discovery. The applicability of the method to other drug targets is also considered. |
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