ITR/AP (BIO) Computational tools for determining the 3-D static and dynamic structure of viruses

Purdue University, West Lafayette IN

Investigators

Abstract

ITR Proposal 0112672, Doerschuk Abstract Understanding the dynamical behavior of virus particles, e.g., the self assembly and subsequent maturation steps that lead to an infectious virus particle, is a key challenge in basic biology (e.g., the understanding of protein-nucleic acid interactions) and in medicine (e.g., the development of drugs that interfere with viral replication). This research contributes to that goal by developing new computational tools for structural biology, emphasizing experimental approaches appropriate for the study of dynamics and emphasizing the bi-directional interplay of new structural biology problems and new formulations of existing structural biology problems with the development of new computational tools. Models and computation for new types of experiments are under development, e.g., x-ray scattering from solutions of labeled viral particles which are oriented by immersion in a strong electric field thereby transforming solution scattering to something analogous to the more informative fiber diffraction. New computational approaches to standard problems are also under development, e.g., phase retrieval for the x-ray crystallography of particles with non-crystallographic symmetries based on iterative phase retrieval algorithms applied to lattices that are computationally oversampled by interpolators based on the symmetry. Computational areas involved include fast 3-D Radon transform algorithms, a component of computing the cryo electron micrograph predicted from a given virus structure, and global optimization, in order to improve the values of the parameters that describe the virus structure. The PIs have a long term interest in undergraduate involvement in research and financial support for undergraduate research assistants is included.