Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

Brownian Dynamics of Superhelical DNA

The processes by which DNA carries out its basic functions require both local transformations of its familiar double-helical structure and global deformations of its axis curve. The molecule?s topology, which couples these events, plays a central role in all fundamental biological processes involving DNA -- the transcription of genes, the replication and recombination of chromosomes, and the repair of DNA damage -- in organisms at all levels of complexity. We have developed computational methods for Brownian dynamics simulations of scenarios in which the topology of DNA is dynamically altered by its interactions with proteins (1-3). We will present results from simulations performed at two levels of resolution. At the first level, double-helical DNA is represented as a segmented bead-chain, whose subunits approximate the mechanical, topological, and hydrodynamic properties of double-stranded DNA (dsDNA) (1). In this representation, we simulate the formation of a transcription-driven twin-supercoiled domain, in which a bow of positive supercoils is generated downstream and a wake of negative supercoils upstream from the transcription complex. Although this model captures several features of twin-domain formation, it is incapable of resolving sequence-dependent events, such as localized, superhelical stress-induced duplex destabilization (SIDD). At the second level of resolution, the two polynucleotides constituting dsDNA are explicitly represented as two bead-chains that interact via an interstrand potential that includes sequence energetics and captures SIDD (2, 3). In this representation, we simulate the stress-induced melting of a short region of dsDNA intergenic to divergently oriented sites of ongoing transcription. Our results demonstrate the potential of this method both to predict locations of SIDD within a dynamic context and to provide information pertaining to the mechanics of dynamically superhelical systems.

References and Footnotes
  1. S. P. Mielke, W. H. Fink, V. V. Krishnan, N. Grønbech-Jensen, and C. J. Benham. J. Chem. Phys. 121, 8104 (2004).
  2. S. P. Mielke, N. Grønbech-Jensen, V. V. Krishnan, W. H. Fink, and C. J. Benham. J. Chem. Phys. 123, 124911 (2005).
  3. S. P. Mielke and V. V. Krishnan. Research Trends: Trends in Chemical Physics, in press (2006).

Steven P. Mielke*
Craig J. Benham

UC Davis Genome Center
University of California
Davis, CA 95616

*Phone: (530) 902-7198
Fax: (530) 754-9658
Email: spmielke@ucdavis.edu