Multiscale Method for Simulating Protein-DNA Complexes

We present a multiresolution approach to modeling complexes between protein and DNA that contain looped or coiled DNA. The approach combines a coarse-grained model of the DNA loop, based on the classical theory of elasticity, with an atom level model of proteins and protein-DNA interfaces based on molecular dynamics. The coarse-grained DNA description is controlled through the atom level protein description and vice versa. The feasibility of the resulting multiscale modeling approach is demonstrated for a protein-DNA complex in which a protein called the E. colilac repressor forces DNA into a 76 base pair loop. The required simulation involves 230,000 atoms, a number that would triple if both protein and DNA loops were described at the atomic level.