MODELING PROTEIN STRUCTURE USING SPARSE NMR CONSTRAINTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. It has been difficult to obtain experimental structural information on many of the proteins important in the synthesis of cell-surface oligosaccharides (glycosyltransferases, for example). Yet, many of these proteins show strong hits from computational threading programs, some structures can be homology modeled, and others can be predicted from well designed force fields. The goal of this project is to explore the use of residual dipolar coupling (RDC) restraints and paramagnetic distance restraints in improving the efficiency of searches and the quality of the structures that result. The Research Resource will be providing RDC and distance data on model proteins, as well as glycosyltransferases, to the computational groups such as the Baker group at the University of Washington, so that they can modify their approaches to accommodate the inclusion of these types of NMR data. The goal is to develop methods for structure determination that can work with challenging proteins for which only limited amounts of structural data can be obtained.