Enhanced 3D Processing of Spherical and Non-Spherical Virus Structures at High Resolution

Purdue Research Foundation, West Lafayette IN

Investigators

Abstract

ABSTRACT 9986316 Dan C. Marinescu Purdue University Enhanced 3D Processing of Spherical and Non-Spherical Virus Structures at High Resolution Although advances in X-ray crystallography and NMR spectroscopy have made it possible to routinely obtain atomic resolution structures of small to medium sized biological macromolecules, there have not been equivalent advances in high resolution structural studies of large macromolecular complexes. For example, the structure determination of a virus by cryo-transmission-electron microscopy typically takes weeks or months to complete, produces relatively low resolution electron density maps, and has mainly been limited to particles with high symmetry. High resolution structures of such large complexes are essential for understanding cell biology. With support from the National Science Foundation, methods to increase the speed of three dimensional image reconstructions and to generalize the techniques to particles with low symmetry will be developed. These new computational techniques will take advantage of advances in image acquisition combined with high performance computing and parallel computer algorithms. A scaleable computing solution capable of coping not only with existing imaging technology but also with its projected evolution over the next decade will be developed. Parallel algorithms for the determination of the orientation of particle projections and for three-dimensional reconstruction will also be developed. Finally, algorithms and programs for detecting particle positions in electron micrographs will be improved. All of these programs will be developed for inexpensive clusters of personal computers. Development of these algorithms will provide biologists with a computationally fast method to obtain high resolution structures of large macromolecular complexes. A more complete understanding of life processes at the molecular level awaits high resolution analysis of hundreds if not thousands of such complexes. This award will also support the training of computer scientists in biological imaging.