CAREER: Assessment of the Structural Novelty of an Unknown Protein Using Unassigned Residual Dipolar Coupling Data

University South Carolina Research Foundation, Columbia SC

Investigators

Abstract

The objective of this CAREER project is to develop rapid methods of extracting structural information from unassigned NMR data in a computationally efficient manner. More specifically, Probability Density Profile Analysis (PDPA) will be developed. PDPA will utilize Residual Dipolar Coupling (RDC) data that can be acquired very rapidly and accurately by Nuclear Magnetic Resonance spectroscopy. This project will address the main obstacles impeding the realization of the full potential for computational means for protein structure prediction. At this time, at least two major problems are preventing the transition from a purely-experimental to a purely-computational mode of protein structure determination. First, a slow discovery of novel protein folds (20-50 years to complete a vital library of folds), and second current computational tools provide little to no benefit to the community of structural biologists. PDPA exhibits the potential to address these two disparate problems. Such a method can increase the efficiency of selecting novel protein targets by structural genomic centers and therefore reducing the time required for completion of an exhaustive library of protein folds. In addition, such a method will provide the means of experimentally validating computed protein structures and therefore provide a means of protein structure determination other than NMR and X-ray crystallography. This application of PDPA should be of great interest to the universal community of structural biologists of the twenty-first century. Current lack of familiarity of students with areas of computational biology and bioinformatics poses a great impediment in attracting students for research in this field and, consequently, in the advancement of the field. This project will integrate graduate and undergraduate researchers from various disciplines to alleviate this problem. Moreover, combination of the proposed courses, annual competitions, summer short courses, and student exchange programs is expected to increase students' level of awareness and participation in research related to the field. Furthermore, the above mentioned programs are anticipated to facilitate intercollegiate collaboration and recruitment of under represented students and faculty into this research work.