Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

Development of a Coarse Grain Model of the Nucleosome

There have been significant advances and interest in developing coarse grained models of DNA based on elastic rod theories. These models have focused largely on describing the physical-mechanical behavior of the DNA itself, without protein. Here we utilize coarse-grain models for both DNA and protein molecules to investigate the interaction of DNA with protein-complexes. We have focused our attention on the level of detail required in the coarse graining to achieve large scale deformations of the DNA. For this purpose we have chosen the nucleosome, a histone-DNA complex as our example system because (a) there is significant deformation of DNA in the bound state as compared to the free state (i.e., 1.75 turns of a superhelix), (b) the DNA in the complex is on the order of one persistence length, and (c) there are no sequence specific contacts between the protein and the DNA. These three features perhaps make this system a right candidate to be described by the physical-mechanical behavior of DNA.

In our model of the nucleosome the DNA is represented, numerically, as a continuous elastic rod with a continuous charge distribution interacting with a multipolar representation of the electrostatic potential for the nucleosome's histone core. A contact (non-penetration) constraint is also included to account for the histone excluded volume. The conformation of DNA after numerical optimization is compared to the conformation of DNA in x-ray structures of the nucleosome to determine the accuracy of the model. Using this model we have investigated whether the physical basis of superhelical formation arises from DNA self-contact(avoidance), from interaction of DNA with the histone core or from intrinsic properties of the DNA itself.

Sachin Goyal1
Apostol Gramada2
Thomas C. Bishop3, *

1Applied Ocean Physics & Engineering
Woods Hole Oceanographic Institution
Woods Hole, Ma.
2Department of Pharmacology
University of California at San Diego
La Jolla, CA
3Department of Environmental Health Sciences
Tulane University School of Public Health and Tropical Medicine
1440 Canal Street, Suite 2100
New Orleans, La 70112

*Phone: 504-988-6203
Fax: 504-988-1726
Email: bishop@tulane.edu