Brooks 9503998 The objective of this proposal is the development novel and efficient computational approaches to free energy perturbation (FEP) calculations. FEP calculations, carried out extensively on high performance parallel computing systems, hold a great potential for assisting the unraveling of questions regarding structure, dynamics and thermodynamics of biological macromolecules. In this project they will (a) explore the development of new extended sytem methods for chemical FEP calculations which allow the conventional variables associated with "progress" in the chemical coordinates to evolve dynamically; (b) systematically determine an umbrella or biasing potential used in sampling, (c) develop new techiques to further extend and automate the processing methods and advance the error analysis capabilities of weighted histogram analysis method.
