We expand Sculpt, an interactive protein modeling system, to model general (non-protein) molecules and to improve its modeling capabilities. Our objective is to create interactive graphical modeling systems for de novo building and docking of flexible ligands into flexible receptors while maintaining the following: 1. Physically realistic properties and energetics; 2. Interactive calculation of the solvent-accessible surface; 3 - 3. Empirical solvation model; 4. Visualization of electrostatics and time-varying properties through texture mapping. Phase I demonstrates feasibility of this modeling system by addressing two problems: (1) specifying a molecular model of arbitrary molecules, and (2) interactively calculating the solvent-accessible surface for use in solvation and visualization. We investigate several methods for transforming molecular coordinates and bond topology into Sculpt's unique molecular specifications. We modify an algorithm that determines a solvent-accessible surface to improve its performance by a factor of four. Our system should significantly reduce the time for generation of lead compounds and refinement of small molecules and should enhance the understanding of ligand-receptor and protein-protein interactions. This work will directly produce commercial applications for structure-based and de novo design of small molecules, site-directed mutagenesis experiments, protein structure predictions, database screening, and education.
This work will directly produce commercial applications for structure-based and de novo design of small molecules, site-directed mutagenesis experiments, protein structure predictions, database screening, and education.
