Research Project
3509058
DESCRIPTION (Adapted from applicant's abstract): The plan is to develop software for a personal computer and a graphics workstation 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. In its 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. Unlike other existing algorithms, this docking software will explicitly include flexibility of protein surface sidechains. This method would exploit an automated force-guided search which would avoid trapping in local energy minima, and would further allow the user to manipulate the conformers with full energy monitorization. Phase Il will add user intervention to the Brownian force-guided docking algorithm and the ability to calculate both rates and equilibrium constants of docking two macromolecules into user- specified geometries.
