The general purpose of this work is to study the physical chemistry of solutions of the nucleic acids, particularly DNA. Emphasis will be placed on those aspects of particular importance in laboratory practice. We propose to examine the effects of the charge of the macromolecule on its sedimentation rate and on its diffusion coefficients, both translational and rotational. This will be done using the theory of polyelectrolytes and working out the solutions of the equations on a computer. We will do both experimental and theoretical work on the degradation of long DNA molecules by high flow rates. The experimental work will examine DNA molecules of different molecular weights both in steady and in non-steady flows, both laminar and extensional. The theoretical part will use computer simulation of the motions of a string-of-beads model at high flow rates to examine the distribution of chain configurations and of forces in the chain, and how these change with time. The third part of the work will be an attempt to develop a detailed understanding of the molecular mechanisms of gel electrophoresis, particularly with regard to the dynamic processes involved in the migration of chain molecules through gels. This would be done partly by computer simulation, and partly by measurement of quantities indicative of the mechanisms involved in the migration. Such quantities would be dichroism of DNA in a gel, which would indicate orientation changes during migration, and migrations transverse to the electric field, indicative of the tortuosity of the paths of the molecules through the gel.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM011916-22
Application #
3268318
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1977-01-01
Project End
1986-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
22
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Nichols, W L; Zimm, B H; Ten Eyck, L F (1997) Conformation-invariant structures of the alpha1beta1 human hemoglobin dimer. J Mol Biol 270:598-615
Zimm, B H; Levene, S D (1992) Problems and prospects in the theory of gel electrophoresis of DNA. Q Rev Biophys 25:171-204
Levene, S D; Zimm, B H (1989) Understanding the anomalous electrophoresis of bent DNA molecules: a reptation model. Science 245:396-9
Conrad, J; Troll, M; Zimm, B H (1988) Ions around DNA: Monte Carlo estimates of distribution with improved electrostatic potentials. Biopolymers 27:1711-32
Levene, S D; Zimm, B H (1987) Separations of open-circular DNA using pulsed-field electrophoresis. Proc Natl Acad Sci U S A 84:4054-7
Lumpkin, O J; Dejardin, P; Zimm, B H (1985) Theory of gel electrophoresis of DNA. Biopolymers 24:1573-93