Abstract

The hope of understanding relationships between structure and function is at the heart of research in structural biology. At the macromolecular level, only computer models are capable of handling the enormous number of interactions that determine structure and dynamics. This project is aimed at elucidating the principles that determine how DNA sequence affects DNA structure and how that structure is affected by biologically relevant environmental factors, such as closure into circles, supercoiling, and interactions with proteins and drug molecules. Computer models are being developed for investigating these problems. Among these is a general purpose program for predicting and analyzing DNA structure when the sequence is specified. Also under development is a new program for modeling DNA supercoiling in molecules up to about 5000 basepairs long, with structural resolution to the basepair level. It will be used to investigate the effects of sequence, supercoiling pressure, and protein binding on global and local structure. New algorithms are being developed for the treatment of electrostatic effects, for the simplified treatment of solvation, for modeling conformational transitions, and for carrying out molecular dynamics simulations on general purpose parallel computers.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM034015-05
Application #
3284390
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1985-09-06
Project End
1993-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Alabama Birmingham
Department
Type
School of Medicine & Dentistry
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294

  Publications

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
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
Leontis, N B; Piotto, M E; Hills, M T et al. (1995) Structural studies of DNA three-way junctions. Methods Enzymol 261:183-207
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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