COMPUTER-ASSISTED PEPTIDE DESIGN

THE LONG-TERM OBJECTIVE IS TO APPLY STATE-OF-THE-ART COMPUTER SIMULATION SOFTWARE TECHNIQUES, INCLUDING MOLECULARDYNAMICS, MOLECULAR MECHANICS, AND INTERACTIVE GRAPHICS ANALYSIS, TO THE UNDERSTANDING OF THE CONFORMATIONAL PREFERENCES OF BIOLOGICALLY ACTIVE PEPTIDES TO GUIDE AND STIMULATE THE DESIGN OF PEPTIDE AND NONPEPTIDE ANALOGS THAT BLOCK THE ACTIVITY OF THE PEPTIDE AT THE RECEPTOR. FEATURES OF THE CONFORMATIONAL PREFERENCES OF PEPTIDES THAT THIS RESEARCH SEEKS TO UNDERSTAND THROUGH MODELING CAN BE MAPPED FOR THE MOST PART WITH SIMPLE METRIC DESCRIPTORS. PHASE I OBJECTIVES ARE TO DEVELOP AND IMPLEMENT NEW CONFORMATIONAL ANALYSIS ALGORITHMS FOR PEPTIDES THAT UTILIZEA DISTANCE MATRIX (I.E., METRIC) REPRESENTATION OF THE MOLECULE; TO SEARCH THE CONFORMATIONAL SPACE AVAILABLE TO THE PEPTIDE ENDOTHELIN USING MOLECULAR DYNAMICS SIMULATION AT ELEVATED TEMPERATURES AND ANALYZE THE CONFORMATIONAL SPACE AVAILABLE TO THIS PEPTIDE HORMONE; AND TO SEEK COLLABORATIVE AGREEMENTS WITH CHEMICAL SYNTHESIS/BIOLOGICAL TESTING GROUPS SEEKING TO DEVELOP ANALOGS OF THIS PEPTIDE. PHASE II RESEARCH WILL INVOLVE INVESTIGATIONS OF ANALOGS OF ENDOTHELIN, ANF, AND OTHER PEPTIDES.