The research may be divided into two major categories: I. Studies on the solution structure of DNA and on the changes it undergoes upon interaction with ions, polyamines and proteins. More specifically, we will be studying: 1) the collapse of DNA in the presence of polyamines and polyamine homologs. Techniques used are flow linear dichroism, fiber diffraction techniques, quasi-elastic light scattering and circular dichroism. 2) Investigations of the effect of ion binding and intercalation on the flexibility and structure of DNA in solution. 3) Protein-DNA interaction. The main object is to use optical-hydrodynamic techniques such as streaming linear dichroism and quasielastic light scattering to elucidate the structural changes undergone by the DNA as a result of these interactions. Early systems to be studied are the higher structure of chromatin and single stranded DNA saturated with the gene 32 protein of phage T4. These studies will be accompanied by theoretical and spectroscopic investigations on the optical, mechanical and statistical properties of DNA. II. Studies of mutant T4 lysozymes. Temperature sensitive and other mutations of phage T4 lysozyme are to be studied in solution as a function of known point mutations.
The aim i s to elucidate the nature of the interactions which cause spontaneous folding. The work will include studies of the thermodynamics of stabilization. Since we now believe the temperature sensitivity may be connected with enhanced structural fluctuations rather than structural changes, we will be investigating this aspect by studying the sensitivity to proteolytic degradation and hydrogen exchange techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM020195-28
Application #
3269929
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1978-04-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
28
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Oregon
Department
Type
Graduate Schools
DUNS #
948117312
City
Eugene
State
OR
Country
United States
Zip Code
97403
Qian, H (1994) A thermodynamic model for the helix-coil transition coupled to dimerization of short coiled-coil peptides. Biophys J 67:349-55
Schellman, J A (1994) The thermodynamics of solvent exchange. Biopolymers 34:1015-26
Anderson, D E; Hurley, J H; Nicholson, H et al. (1993) Hydrophobic core repacking and aromatic-aromatic interaction in the thermostable mutant of T4 lysozyme Ser 117-->Phe. Protein Sci 2:1285-90
Qian, H (1993) Single-residue substitution in homopolypeptides: perturbative helix-coil theory at a single site. Biopolymers 33:1605-16
Scholtz, J M; Qian, H; Robbins, V H et al. (1993) The energetics of ion-pair and hydrogen-bonding interactions in a helical peptide. Biochemistry 32:9668-76
Chen, B L; Baase, W A; Nicholson, H et al. (1992) Folding kinetics of T4 lysozyme and nine mutants at 12 degrees C. Biochemistry 31:1464-76
Bell, J A; Becktel, W J; Sauer, U et al. (1992) Dissection of helix capping in T4 lysozyme by structural and thermodynamic analysis of six amino acid substitutions at Thr 59. Biochemistry 31:3590-6
Hurley, J H; Baase, W A; Matthews, B W (1992) Design and structural analysis of alternative hydrophobic core packing arrangements in bacteriophage T4 lysozyme. J Mol Biol 224:1143-59
Daopin, S; Alber, T; Baase, W A et al. (1991) Structural and thermodynamic analysis of the packing of two alpha-helices in bacteriophage T4 lysozyme. J Mol Biol 221:647-67
Dao-pin, S; Soderlind, E; Baase, W A et al. (1991) Cumulative site-directed charge-change replacements in bacteriophage T4 lysozyme suggest that long-range electrostatic interactions contribute little to protein stability. J Mol Biol 221:873-87

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