Contribution of Nonlinear effects into DNA structural transformations and Mechanical Properties

Start Date: 09/01/2008
End Date: 08/01/2010

It is recognized now that some of biologically important and experimentally verified properties of DNA such as nucleation of denaturation bubbles, double-helix opening and conformational A<->B transitions can not be fully and quantitatively understood and theoretically described without taking into account the essentially nonlinear effects. One of the main characteristic features of these effects is their cooperative nature. The broad goal of the Project is the elucidation of underlying molecular mechanisms of such cooperativity. To accomplish this goal we will have to develop an appropriate set of theoretical tools and models. Atomistic simulations do, in principle, contain the required information, but are not well suited for the task due to the very large number of the degrees of freedom involved at this level of DNA description. Coarse-grained description generally simplifies the problem, but existing coarse-grained DNA models can not provide an adequate analytical description of the structural transformations responsible of the effects mentioned above. This is because the common analytical approaches have turned out to be applicable for very simplified one- and two-component DNA models. Our interdisciplinary team proposes to address these problems by new 3D coarse-grained model that will fully account for the nonlinear effects in the DNA deformation and will admit an analytical study due to special technique elaborated by Russian team. The model will be constructed based on the feedback from all-atomic molecular-dynamic simulations and will be validated against available experimental data. The study will complement experiment by addressing, through novel computational methods, the fundamental question of the origin and physical nature of structural transformations of the DNA double helix most relevant biologically. The model will be constructed based on the feedback from all-atomic molecular-dynamic simulations and will be validated against available experimental data.

The study will complement experiment by addressing, through novel analytical and computational methods, the fundamental question of the origin and physical nature of structural transformations of the DNA double helix. These properties are important for our understanding of the main (informational) function of the DNA. The research will have a broad impact in the field of molecular biophysics since it offers a unique perspective on the fundamental properties of the DNA - perhaps the most important molecule in biology.

Grant Institution: Civilian Research and Development Foundation

Amount: $30,000

People associated with this grant:

Alexey Onufriev