Major advances in the understanding of macromolecular structure have come directly from advances in computation and computer graphics and from the development of methods that have enhanced collection of X-ray crystallographic data. This award will support a collaborative effort to solve major problems in crystallographic refinement and computer graphics analysis of macromolecular structure using the combined unique resources available at the San Diego Supercomputer Center (SDSC), the University of California at San Diego (UCSD), and the Research Institute of Scripps Clinic (RISC). Each institution has outstanding strengths in aspects of crystallography, molecular dynamics, graphics, and computation. In Crystallography, the group expects to decrease the time required to refine a structure from years to months, and to substantially improve the accuracy of the refinement. Tightly coupling supercomputer calculations on the CRAY with visualization of the calculation on a graphics workstation will allow the design and testing of novel molecular modeling algorithms. Algorithm design will be driven and tested by specific structural problems requiring the analysis of folding, shape, flexibility, and electrostatic forces as well as the prediction of interaction complexes. This project will provide a set of integrated software tools that will result in advances in structure determination and refinement, and in structural interpretation, modeling, and design. The intention is to develop a facility that can be widely used by the scientific community as a whole. This project should have a major impact on the efficient use of supercomputer calculations for structural molecular biology and molecular graphics.
