Manipulating Proteins Through Interactive Simulation

The long-term objective of this work is to build interactive computer software that lets usersdirectly modify a protein's three-dimensional structure while the software maintains valid physicalproperties such as van der Waals separations, peptide geometry, and hydrogen bonds. This builds onSculpt, a prototype graphical modeling system that maintains many protein properties as oneinteractively moves atoms. Phase I adds the following interactive capabilities through mathematicalanalysis and algorithm development: 1. edit protein topology interactively allowing residue insertion,deletion, and substitution; 2. assemble multiple chains (e.g. from homology) with valid peptide geometry;3. decompose a model into regions with restricted, limited, or unrestricted atom motions; 4. movesecondary structure directly while modeling sidechain interactions with other atoms; 5. modelelectrostatic interactions. Phase II further develops these algorithms and concentrates on interfaceissues. This will directly produce commercial software for protein modeling and develop a foundationfor later products in crystallography, de novo drug design, structure determination based on NMR,nucleotide modeling, and education.