The main thrust of this research concerns computer simulations of biological molecules. A new class of Monte Carlo simulations has been developed by the principal investigator which (slightly) relaxes the usual Markovian constraint to enable greatly improved efficiency for systems with important inhomogeneity and local anisotropy. These new and quite general methods will be used to investigate models of biological molecules. The research will study equilibrium fluctuations of such molecules and continue work on the protein folding problem. Calculations of free-energy differences and potentials of mean force will be carried out using multiple histogram techniques developed by the principal investigator. Another important area of application is the determination of the structure of biological molecules from x-ray scattering. One of the most effective current methods of optimizing the fit of the structure of x-ray data involves simulated annealing with molecular dynamics. The application of new Monte Carlo simulation methods has promise of improving the efficiency of some of these structure determinations. The award is funded jointly by the Materials Theory program in the Division of MAterials Research and the Computational Biology Activity in the Division of Biological Instrumentation and Resources. %%% This computational research will focus on algorithm development for Monte Carlo simulation and applications to problems of biological importance. Simulations will be done on the behavior of biological molecules and the folding of proteins. The research has great potential should these new Monte Carlo simulations be shown to be competitive with conventional molecular dynamics techniques. The research is jointly funded by the Materials Theory program and the Computational Biology Activity.
