Our objective is to study the effects of the high charge of the DNA molecule on its physico-chemical properties and behaviour. A major part of the work will be concerned with the gel electrophoresis of DNA. Gel electrophoresis is the most widely used physical technique in DNA research, but it is very poorly understood at the molecular level. The technique is very effective for separating and analyzing small DNA molecules, but loses effectiveness rapidly when used in the conventional way with molecules from the larger viruses, and is practically useless with chromosome-sized DNA. It is important to get a better understanding of why it fails with large DNA, and why the recently introduced filed-switching method of Schwartz and Cantor mitigates this problem.
Specific aims are: to extend the recently published preliminary theory to the field-switching case, to carry out experiments with field switching and to compare the results to theory, to develop a computer simulation of the molecular processes in the gel electrophoresis of DNA, to relate the gel electrophoresis of DNA to that of proteins. A smaller part of the project is to use computer simulation to find out to what extent the small ions around the DNA helix are in the minor or major grooves, near the phosphates, or form a chaotic cloud.
|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|