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.
