The specific aim of this project is to gain an understanding of how interatomic interactions determine the relative stabilities of alpha, beta, and beta-turn structures, and to show how this information will be used to identify chain-folding-initiation sites (CFIS) and how it will be incorporated into a protein folding algorithm. The helix-forming tendency will be determined for cysteine/cystine, the last of the 20 naturally occurring amino acids for which this information will have been obtained. The beta <--> coil theory will be extended from a homopolymer to a specific-sequence copolymer, and experiments will be carried out (within the framework of this theory) to determine the tendencies of the naturally occurring amino acid residues to form beta-sheets and beta- turns. The experimental results (a) will provide important information as to how short-range intra-residue interactions determine the intrinsic conformational preferences of the naturally occurring amino acid residues; (b) will enable one to assess the role of such interactions in stabilizing local ordered structures among several adjacent residues, e.g., CFIS that are important in protein folding; (c) will provide an essential ingredient for procedures to overcome the multiple-minima problem in protein folding algorithms; and (d) will provide an understanding of the role of conformation in: (1) diseases related to mutations, and in (2) site-directed mutagenesis in recombinant DNA methods. They will also structure from a 36-residue protein to proteins containing of the order of 100 residues.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK008465-24
Application #
3224569
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1979-01-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
24
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Cornell University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850