It is generally accepted that the amino acid sequence of a protein determines its ultimate three-dimensional structure. Researchers have noted that certain amino acids have a preference for a given secondary structure, and a number of schemes have been developed that use amino acid preferences to predict secondary structure from primary sequence. However, twenty years of research has led to little improvement over the original predictive schemes, and today theory remains about 70 percent accurate. During the last granting period, it was shown that in addition to considering the sequence of amino acids, the environment seen by the sequence (or bulk solvent in the peptides under study) must also be considered. Apparently, predictive algorithms must take the microsolvent of non-local amino acids in the tertiary structure into account when predicting secondary structure. The alpha-helix nucleation hypothesis was also investigated; a hypothesis that states that only a few residues with a strong propensity for alpha-helix structure initiate its formation and propagate the structure through indifferent sequences until strong breakers terminate the growth on both ends. The system investigated did not obey the nucleation hypothesis, indicating that the average propensity of near neighbors for secondary structure drive its formation. The first two specific aims listed here are the obvious sequels to the research carried out over the past granting period. The last specific aim continues the long standing interest of Dr. Johnson in relating the circular dichroism of proteins to their secondary structure, but this is a secondary goal. 1. It is proposed to investigate the conformational preferences of each amino acid in the solvent systems that have been used to stabilize alpha-helix and beta-strand structures. 2. It is proposed to investigate what changes in amino acid preferences are necessary for indifferent sequences to form an alpha helix or a beta-strand. 3. It is proposed to use circular dichroism to investigate the secondary structure of proteins of current interest, and to improve the system of analyzing CD for secondary structure.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Special Emphasis Panel (ZRG3-BBCA (01))
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Oregon State University
Schools of Arts and Sciences
United States
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Macdonald, J R; Johnson Jr, W C (2001) Environmental features are important in determining protein secondary structure. Protein Sci 10:1172-7
Krittanai, C; Johnson Jr, W C (2000) The relative order of helical propensity of amino acids changes with solvent environment. Proteins 39:132-41
King, S M; Johnson, W C (1999) Assigning secondary structure from protein coordinate data. Proteins 35:313-20
Johnson, W C (1999) Analyzing protein circular dichroism spectra for accurate secondary structures. Proteins 35:307-12
Krittanai, C; Johnson, W C (1997) Correcting the circular dichroism spectra of peptides for contributions of absorbing side chains. Anal Biochem 253:57-64
Johnson Jr, W C; Palczewski, K; Gorczyca, W A et al. (1997) Calcium binding to recoverin: implications for secondary structure and membrane association. Biochim Biophys Acta 1342:164-74
Zhong, L; Putnam, R J; Johnson Jr, W C et al. (1995) Design and synthesis of amphipathic antimicrobial peptides. Int J Pept Protein Res 45:337-47
Hirschberg, B T; Mosser, V A; Peterson, G L et al. (1995) Kinetic and biophysical analysis of the m2 muscarinic receptor. Life Sci 56:907-13
Peterson, G L; Toumadje, A; Johnson Jr, W C et al. (1995) Purification of recombinant porcine m2 muscarinic acetylcholine receptor from Chinese hamster ovary cells. Circular dichroism spectra and ligand binding properties. J Biol Chem 270:17808-14
Bloemendal, M; Johnson Jr, W C (1995) Structural information on proteins from circular dichroism spectroscopy possibilities and limitations. Pharm Biotechnol 7:65-100

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