PREDICTION AND DISPLAY OF INTERACTIONS OF MACROMOLECULES

THIS PROJECT WILL DEVELOP SOFTWARE FOR A PERSONAL COMPUTER IN WHICH THE USER CAN INTERACTIVELY DISPLAY THE THREE-DIMENSIONAL STRUCTURE OF DOCKED BIOMOLECULES, INCLUDING PROTEINS AND NUCLEIC ACIDS, AND SIMULTANEOUSLY DISPLAY ENERGETIC PROPERTIES OF THE DOCKING INTERACTION. INITS SIMPLEST APPLICATION, THE SOFTWARE WOULD ALLOW THE USER, STARTING FROM DOWNLOADED COORDINATES, TO COMPUTE AND DISPLAY PHYSICAL PROPERTIES OF INDIVIDUAL BIOMOLECULES, INCLUDING SURROUNDING ELECTROSTATIC FIELDS AND OTHER QUANTITIES. IN ITS MOST ADVANCED APPLICATION, AN EXHAUSTIVE SEARCH OF PLAUSIBLE LOW-ENERGY PROTEIN-LIGAND, PROTEIN-PROTEIN, OR PROTEIN-DNA DOCKING COMPLEXES WOULD BE GENERATED USING A BROWNIAN DYNAMICS ALGORITHM. THIS METHOD WOULD EXPLOIT AN AUTOMATED FORCE-GUIDED SEARCH THAT WOULD AVOID TRAPPING IN LOCAL ENERGY MINIMA AND WOULD FURTHER ALLOW THE USER TO MANIPULATE THE CONFORMERS WITH FULL-ENERGY MONITORIZATION. PHASE I WORK WILL DEMONSTRATE WHETHER A CODE OF SUCH SOPHISTICATION CAN (1) BE INTEGRATED TO RUN ON A PERSONAL COMPUTER, (2) WITHSTAND THE SIMPLIFYING APPROXIMATIONS NECESSARY TO ADAPT IT TO THIS ENVIRONMENT, AND (3) ACCURATELY REPRODUCE RESULTS OBTAINED BY MAINFRAMES. THIS PHASE I TEST VERSION ON PROTEINS WOULD BE GENERALIZED IN PHASE II TO NUCLEIC ACIDS WITH ADDITIONAL USER-FRIENDLY FRONT-END INTERFACING.