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.
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