A one nanosecond molecular dynamics simulation of the glucocorticoid receptor protein in complex with a...

We investigated protein/DNA interactions, using molecular dynamics simulations computed for one nanosecond, between a 10 Angstom water layer model of the glucocorticoid receptor (GR) DNA binding domain (DBD) amino acids and DNA of a glucocorticoid receptor response element (GRE) consisting of 29 nucleotide base pairs. Hydrogen bonding interactions were monitored. In addition, van der Waals and electrostatic interaction energies were calculated. Amino acids of the GR DBD DNA recognition helix formed both direct and water mediated hydrogen bonds at cognate codon-anticodon nucleotide base and backbone sites within the GRE DNA right major groove halfsite. Likewise amino acids in a beta strand structure adjacent to the DNA recognition helix formed both direct and water mediated hydrogen bonds at cognate codon-anticodon nucleotide base and backbone sites within both the GRE right and left major groove halfsites. In addition, amino acids within a predicted alpha helix located on the carboxyl terminus of the GR DBD interacted at codon-anticodon nucleotide sites on the DNA backbone of the GRE right major groove flanking nucleotides. These interactions together induced breakage of Watson-Crick nucleotide base pairing hydrogen bonds, resulting in significant structural changes and bending of the DNA into the protein.