The goal of the proposed research proposal is to apply a promising new computational technique, the Weighted-Ensemble method, to the study of the kinetics of the enzyme triose phosphate isomerase. Because this enzyme has been studied extensively it will be a good candidate for the refinement of this technique and the understanding of its strengths and limitations. The Weighted-Ensemble method will be used to link the different types of dynamical simulations appropriate for the different stages along the reaction pathway, and an attempt will be made to match experimental rate constants without using any adjustable parameters in the model. Once this technique is developed further, the savings in computer time for future studies of other enzymes could have a considerable impact on the fields of metabolic engineering and drug design.
