Structural domains in proteins are regions that are thought to fold autonomously. Previous work by the principal investigator has linked domain structure with physical compactness. Large compact units correspond well to domains while small compact units seem to be folding intermediates or possible folding nucleation sites. Small compact units may also serve as useful entities in protein design. This research will study both experimental and theoretical aspects of the compact domain problem. Experimentally, a series of peptides corresponding to compact and noncompact structures will be obtained using solid phase synthesis or chemical cleavage of the native protein. The peptides' structure will be analyzed using circular dichroism and high resolution two-dimensional NMR. If the structure of the compact peptides closely corresponds to that observed for the peptide within the native protein, while the noncompact peptides have little or no structure, then the compact unit theory will be proven. Theoretical work will focus on discontinuous units containing two different polypeptide chains. Recent advances in computer technology and a new approach to performing calculations should make it possible to analyze for discontinuous compact domains. The examination of discontinuous protein domains should provide new insights into protein structure. Once a good theoretical model for discontinuous compact domains is formulated, it will be experimentally tested using a similar methodology to that used for continuous domains.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29GM046664-01
Application #
3468647
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1992-05-01
Project End
1997-04-30
Budget Start
1992-05-01
Budget End
1993-04-30
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Pharmacy
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210