The goal of this research is the development of computer-based models for investigating the influence of DNA sequence on the structure and dynamics of the molecule. Methods to be used include conformational energy calculations, molecular dynamics, normal mode analysis, and computer graphics, including real-time movies. The motions to be studied range from the rapid fluctuations of local structure, such as backbone torsional angles and sugar pucker, to the slower variations of large scale structure, such as bending, twisting, stretching, and breathing of the helix. Correlations between these motions will be investigated, as will their variation as a function of conformation (A-DNA, B-DNA, and Z-DNA). Transitions between the various conformations will also be examined. In all of the foregoing studies, investigations are to be made into the effects of sequence and chemical modification of the bases. This research will lead to an understanding of how sequence determines structure, laying some of the groundwork for research into the problem of how proteins recognize specific DNA sequences, a fundamental problem in understanding the regulation of gene replication and expression.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM034015-03
Application #
3284389
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1985-09-06
Project End
1988-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
School of Medicine & Dentistry
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Sprous, D; Tan, R K; Harvey, S C (1996) Molecular modeling of closed circular DNA thermodynamic ensembles. Biopolymers 39:243-58
Tan, R K; Harvey, S C; Di Mauro, E et al. (1996) DNA topological context affects access to eukaryotic DNA topoisomerase I. J Biomol Struct Dyn 13:855-72
Tan, R K; Sprous, D; Harvey, S C (1996) Molecular dynamics simulations of small DNA plasmids: effects of sequence and supercoiling on intramolecular motions. Biopolymers 39:259-78
Leontis, N B; Piotto, M E; Hills, M T et al. (1995) Structural studies of DNA three-way junctions. Methods Enzymol 261:183-207
Sprous, D; Zacharias, W; Wood, Z A et al. (1995) Dehydrating agents sharply reduce curvature in DNAs containing A tracts. Nucleic Acids Res 23:1816-21
Rudnicki, W R; Lesyng, B; Harvey, S C (1994) Lagrangian molecular dynamics using selected conformational degrees of freedom, with application to the pseudorotation dynamics of furanose rings. Biopolymers 34:383-92
Harvey, S C; Gabb, H A (1993) Conformational transitions using molecular dynamics with minimum biasing. Biopolymers 33:1167-72
Leontis, N B; Hills, M T; Piotto, M et al. (1993) A model for the solution structure of a branched, three-strand DNA complex. J Biomol Struct Dyn 11:215-23
Gabb, H A; Harris, M E; Pandey, N B et al. (1992) Molecular modeling to predict the structural and biological effects of mutations in a highly conserved histone mRNA loop sequence. J Biomol Struct Dyn 9:1119-30
Harvey, S C; Tan, R K (1992) Teaching macromolecular modeling. Biophys J 63:1683-8

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