Molecular modeling has been applied to a variety of problems in the LMC concerned with drug design and inhibition of binding of molecules to receptors. Protein Kinase C. The role of diacyl glycerols as competitive inhibitors of phorbol for the active site of protein kinase C has been studied. The inhibitory effectiveness of such analogs as a function of their molecular shape can now be predicted fairly reliably. Reverse Transcriptase Inhibitors. Modeling of nucleosides which inhibit reverse transcriptase has led to a definition of the molecular requirements for such inhibition. Three-Dimensional Database. Use of the FCRF CRAY to develop this database has been abandoned and methods for accomplishing this work on a super mini- computer at NIH are under development. Tyrosine Kinase. An extensive quantitative structure-activity relationship study of potential tyrosine kinase inhibitors has been completed.
