ALGORITHMS FOR CONFORMATIONAL SEARCH &FREE ENERGY PERTURBATION

Thisresearchisdirectedtowarddevelopinggreatlyimproved methods for sampling phase space in molecular systems having multiple conformations separated by significant energy barriers. The work will be important in obtaining converged free energies from simulations of complex chemical systems. Recently we developed a hybrid simulation system that mixes smart Monte Carlo and stochastic dynamics (MC(JBW)/SD). This method converges complex molecular systems quite rapidly because the Monte Carlo part of the algorithm is directed to preferently sample known low energy regions of conformational space (by Jumping Between Wells). In our MC(JBW)/SD simulation method, the MC(JBW) part of the algorithm operated only is a subset (e.g. torsions) of all available degrees of freedom. This past year we developed a pure MC(JBW) method that samples all degrees of freedom and generates the same ensembles as traditional Metropolis MonteCarlo - only much more rapidly. We have also used quantum mechanics to develop a new parameter set for carbohydrates and used it to compute conformational and anomeric free energies of simple sugars and oligosaccharides.