A ONE NANOSECOND MOLECULAR-DYNAMICS SIMULATION OF THE GLUCOCORTICOID RECEPTOR PROTEIN IN COMPLEX WITH A GLUCOCORTICOID RESPONSE ELEMENT DNA-SEQUENCE IN A 10 ANGSTROM WATER LAYER

We investigated protein/DNA interactions, using molecular dynamics sim ulations computed for one nanosecond, between a 10 Angstom water layer model of the glucocorticoid receptor (GR) DNA binding domain (DBD) am ino 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 interacti on 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 st ructure adjacent to the DNA recognition helix formed both direct and w ater mediated hydrogen bonds at cognate codon-anticodon nucleotide bas e and backbone sires within both the GRE right and left major groove h alfsites. In addition, amino acids within a predicted alpha helix loca ted on the carboxyl terminus of the GR DBD interacted at codon-anticod on nucleotide sites on the DNA backbone of the GRE right major groove flanking nucleotides. These inter actions together induced breakage of Watson-Crick nucleotide base pairing hydrogen bonds, resulting in sig nificant structural changes and bending of the DNA into the protein.