Structure and Dynamics of Proteins from NMR Orientational Data

University Of Georgia Research Foundation Inc, Athens GA

Investigators

Abstract

The continued exploration of a potential source of new information on protein structure and dynamics in solution is proposed. The new information comes from residual dipolar couplings seen in NMR spectra of proteins when they are induced to have low levels of spatial order by their interaction with an anisotropic medium, such as an aqueous liquid crystal, or by their direct interaction with a sufficiently high magnetic field. The easily measured couplings provide an efficient route to information about protein structure and dynamics through their dependence on average interaction vector length and orientation. In addition to basic structural studies of isolated proteins, objectives include, (i) the development and application of a method for defining the geometry of protein-protein interactions in solution, and (ii) the development and application of a strategy for quantifying the amplitudes of internal motions in proteins. The definition of the geometry of protein-protein interaction serves to move structural and mechanistic descriptions from isolated protein domains toward the system wide descriptions that are needed for understanding complete life processes. The quantification of amplitudes of internal motion provides insight into mechanistic details of protein function that might be missed in static representations of structure. The target systems for testing the methodology include a number of well characterized proteins such as myoglobin and rubredoxin, but also include recently identified electron transfer partners of a rubredoxin from a thermophilic organism. In terms of general impact, this project will provide training opportunities for undergraduate, graduate, and postdoctoral students. Development of methods and training in the use of methods that can define protein function at a molecular level is becoming increasingly important in a post-genomic era. Vast quantities of protein sequence information can have an impact on the development of new biotechnology products, and the treatment of disease, but only with an adequate understanding of protein function.