The capabilities of computer-assisted molecular modeling have been expanded in a variety of directions and the techniques have been applied to a number of problems in the LMC concerning drug design, receptor sites, binding to-and inhibition of enzymes. Modeling Studies: The effect of solvent on the stable conformations of various medicinally important molecules has been studied and some understanding of the conformation in solution has been secured. Protein Kinase C: Inhibition of the binding of phorbol to protein kinase C was observed with several ribose-derived gamma-lactones as indicated by models of the compounds. Tyrosine Kinase: The structural requirements in the styrene series for successful inhibition of tyrosine kinase have been established and tested. Reverse Transcriptase Inhibitors: A study of the ring-expanded oxetanocins was completed. One of the synthesized isomers showed anti-HIV activity and the other did not. This result was compatible with the modeling data. Three-Dimensional Database: Approximately half the compounds in the DTP Database have been converted to three-dimensional structures and a distance-based search system has been developed.