Investigating Structure and Topology of Protein-Mediated DNA Loops via Computational Modeling of Elastic Energy

Abstract

Many biological processes involve deformations of DNA 3D structure. DNA looping generated by a protein bound to two distant sites on the double helix is a familiar mechanism employed in regulation of cellular processes. We employ a computational method to obtain minimum energy structures of DNA loops mediated by the Lac repressor protein, whereby the potential energy of elastic deformation is optimized. By evaluating the energy required to deform DNA, we can predict the likely spatial pathway of the DNA strand. By adjusting the optimization parameters, we can evaluate the effects of torsional stress on loop configuration and global topology. For instance, altering the position or orientation of the end constraints provides insight into mechanisms that proteins may use to control DNA folding. Alternatively, changing the chain length of the constrained DNA molecule alters the total twist, which is reflected in the supercoiling of the molecule. Adjusting the intrinsic helical repeat in the optimization simulates changes in the cellular environment such as found with increased salt content. Using knowledge of the cost of deforming base-pair steps of different types we simulate the effect of nucleotide sequence on the overall structure of constrained DNA chains.