We have developed a strategy for efficiently docking a large combinatorial library into a target receptor. For each scaffold orientation, all potential fragments are attached to the scaffold, their interactions with the receptor are individually scored and factorial combinations of fragments are constructed. To test its effectiveness, this approach is compared to two simple control algorithms. ...

The exclusive role of heterocyclic compounds for drug discovery is best documented by the occurrence of a heterocyclic moiety in current drugs; the majority of drugs are heterocyclic compounds. Consequently, a substantial effort has been dedicated to the development of chemistries, both solidand solution-phase, for combinatorial syntheses of heterocyclic libraries. Traditionally, generic combin...

Title of Dissertation: COMBINATORIAL LIBRARY DESIGN OF MUTATIONRESISTANT HIV PROTEASE INHIBITORS. Sripriya Chellappan, Doctor of Philosophy, 2006 Dissertation directed by: Professor Michael K. Gilson Department of Molecular and Cellular Biology The emergence of HIV strains that are resistant to current HIV protease inhibitors in the past few years has become a major concern in AIDS treatment. T...