A Computational Rod Model to Simulate the Mechanics of DNA Looping

A Computational Rod Model to Simulate the Mechanics of DNA Looping


It is well known that the structural deformations (stressed states) of DNA molecule play a crucial role in its biological functions including gene expression. For instance, looping in DNA (often mediated by protein binding) is a crucial step in many gene regulatory mechanisms. Functional involvement of DNA and/or proteins in several diseases is key to their diagnosis and treatment. Therefore the fundamental knowledge of the structure-function relationship may one day pave the way to new discoveries in medical research including future drug therapies.
In this talk, I will focus on an example of protein-mediated looping of DNA that is also widely studied experimentally (see Figure 1 below). We use the ‘mechanical rod' model of DNA molecules to simulate its structural interactions with proteins/ enzymes during gene expression. Our rod model can simulate the nonlinear dynamics of loop/supercoil formation in DNA on “long length scales”. The formulation accounts for the structural stiffness of the DNA strand, its intrinsic curvature, chiral (right-handed helical) construction and has provisions for its physical interactions with the surrounding medium. The simulations of protein-mediated DNA looping illustrate how the mechanical properties of DNA may affect the chemical kinetics of DNA-protein interactions (as depicted in the Figure 1 below) and thereby regulate gene expression.