The objective of this application is to provide a sufficiently powerful computing facility to support the computationally intensive research efforts being undertaken by a number of groups working on the structure function relationships of biological molecules and their assemblies. These research efforts include x-ray crystallographic studies of proteins and macromolecular assemblies, solution structures of proteins and polypeptides by NMR spectroscopy, computational simulation of biomolecular behavior using quantum mechanics, molecular mechanics, and molecular dynamics, molecular modeling of macromolecular interactions using computer graphics and computational analysis and methods development in molecular graphics and computational geometry. The Research Institute of Scripps Clinic and the Department of Molecular Biology, agree to furnish the space and support environment to house the equipment and to guarantee the remaining costs of the machine and its maintenance. The areas of research in which the computer will be used include: 1. High resolution structural characterization of poliovirus and related viruses by x-ray crystallographic methods; 2. X-ray crystallographic characterization of the structural natures of antibody-antigen union and of the structure and function of immunologically important macromolecules; 3. X-ray crystallographic studies of structural stability and conformational change in proteins; 4. Crystallographic studies of metalloproteins; 5. Nuclear magnetic resonance studies of structure and dynamics of peptides and proteins in solution; 6. Nuclear magnetic resonance studies of protein folding initiation events; 7. Computer simulation of two-dimensional NMR data; 8. Development and enhancement of distance geometry methods and refinement procedures for experimental determination of solution conformation; 9. Computational simulation of conformational properties of biopolymers; 10. Computational and computer graphic studies of biomolecular interactions; 11. Development and enhancement of computer graphic techniques for macromolecular modeling.
