This work builds interactive computer software that lets users directly modify a protein's three-dimensional structure while the software maintains valid physical properties such as van der Waals separations, peptide geometry, and hydrogen bonds. This builds on Sculpt, a graphical modeling system that maintains these properties as one interactively moves atoms. Our intent is to maintain valid contacts and conformation while providing the user these additional interactive capabilities: 1. insert, delete, and substitute amino acids and disulfide bonds; 2. assemble chain segments with valid peptide geometry; 3. use interactive molecular mechanics to assist in arranging a valid conformation after the changes in 1 & 2; 4. decompose a model into regions with restricted, limited, or unrestricted atom motions; 5. move, bend, and twist secondary structure directly through an intuite 3D interface while modeling interactions with other atoms; 6. address needs specific to NMR, homology modeling, and de novo design. This Phase 2 proposal develops these algorithms, concentrates on interface issues, and tests the results with real modeling research. This work directly produces commercial software for molecular modeling. It also develops the foundation for software products for de novo drug design, structure determination based on NMR and crystallography, nucleic acid modeling, and education.
This work directly produces commercial software for molecular modeling. It also develops the foundation for software products for de novo drug design, structure determination based on NMR and crystallography- nucleic acid modeling, and education.
