Molecular Dynamics Simulation of a DNA Binding Protein free and in Complex with DNA

Abstract

Molecular dynamics simulations have been performed on the DNA binding domain (DBD) of the glucocorticoid receptor (GR) free in aqueous solution and bound as a dimer to a DNA duplex, also in aqueous solution. The combined information from these simulations provides insights into structural and dynamic consequences for the GR DBD upon binding to the DNA in terms of the specific and nonspecific interactions with DNA and also for the protein-protein interacticons at the dimerisation surface. Comparions are made with experimental data, from ¹H -¹⁵N-NMR, on the backbone dynamics of the DBD monomer free in solution, and with the NMR and X-ray structures of the monomer and complex, respectively. Thermodynamic studies, by free energy perturbation methods, of the binding of the small antiviral agent netropsin to DNA have been successful in reproducing the known preference for this minor groove binder for AT regions of DNA, and will be discussed in the framework of using similar methods to study interactions between GR DBD and different DNA sequences.