Interactive Modeling of Flexible Ligands and Receptors

We expand Sculpt, an interactive protein modeling system, to model general(non-protein) molecules and to improve its modeling capabilities. We will create interactive graphicde novo building and docking of flexible ligands into flexible receptors while maintaining the follorealistic properties and energetics; 2. interactive calculation of the solvent-accessible surface -3model; 4. visualization of electrostatics and time-varying properties through texture mapping. Phasefeasibility of this modeling system by addressing two problems: (1) specifying a molecular model ofand (2) interactively calculating the solvent-accessible surface for use in solvation and visualizatmethods for transforming molecular coordinates and bond topology into Sculpt's unique molecular specmodify an algorithm that determines a solvent-accessible surface to improve its performance by a facshould significantly reduce the time for generation of lead compounds and refinement of small molecuenhance the understanding of ligand-receptor and protein-protein interactions. This work will directapplications for structure-based and de novo design of small molecules, site-directed mutagenesis exstructure predictions, database screening, and education.