Macroscopic Modeling and Simulations of Supercoiled DNA with Bound Proteins

General methods are presented for modeling and simulating DNA molecules with bound proteins on the macromolecular level. These new approaches are motivated by the need for accurate and affordable methods to simulate slow processes (on the millisecond timescale) in DNA/protein systems, such as the large-scale motions involved in the Hin-mediated inversion process. Our approaches, based on the worm-like chain model of long DNA molecules, introduce inhomogeneous potentials for DNA/protein complexes based on available atomic-level structures. Electrostatically, we treat those DNA/protein complexes as sets of effective charges, optimized by our Discrete Surface Charge Optimization (DiSCO) package, in which the charges are distributed on an excluded volume surface that represents the macromolecular complex. We also introduce directional bending potentials as well as non-identical bead hydrodynamics modeling to further mimic the inhomogeneous effects caused by protein binding. These models thus account for basic elements of protein binding effects on DNA local structure while being computational tractable. To validate these models and methods, we reproduce various properties measured by both Monte Carlo methods and experiments. We then apply the developed models to study the Hin-mediated inversion system in long DNA. By simulating supercoiled, circular DNA system with or without bound proteins, we observe significant effects of protein binding on global conformations and long-time dynamics of the DNA on the kilo basepair length.

Click to go back to the publication list