This investigation is concerned with the further development of Nuclear Magnetic Resonance Spectroscopy (NMR) as a method to determine the three-dimensional structures of larger biomolecules in solution. It is only very recently that labeling with stable isotopes and the use of three- and four- dimensional heteronuclear NMR has allowed the structure determination of proteins larger than 10 kDa in solution. Here the solution structure determination of a larger alpha helical proteins. These challenges form the backbone of the proposal and will be approached with improvements in efficiency by using heteronuclear cross polarization, with improvements in resolution by using multiple quantum filters and a larger number of dimensions and with improvements in analysis of key multi-dimensional NMR experiments. %%% Recent developments in the methods of Nuclear Magnetic Resonance Spectroscopy have made possible the determination of the three- dimensional structures of smaller proteins in solution. Three dimensional solution structures are relevant to the understanding of their biological functioning, can convey dynamic information and may be obtained by NMR in cases where other methods fail because of lack of crystals. This proposal describes investigations into the development of more advanced NMR methods to help analyze the solution NMR spectra of larger proteins, nucleic acids and complexes thereof. The studies will be carried out with a medium- sized protein as a model system. The new methods will make NMR structure determination possible for larger proteins and nucleic acids and thus contribute to the better understanding of structure and function in this larger class of biomolecules.

Agency
National Science Foundation (NSF)
Institute
Division of Molecular and Cellular Biosciences (MCB)
Application #
9218573
Program Officer
Kamal Shukla
Project Start
Project End
Budget Start
1993-01-01
Budget End
1995-12-31
Support Year
Fiscal Year
1992
Total Cost
$300,000
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109