Book of Abstracts: Albany 2005
A One Nanosecond Particle Mesh Ewald (PME) Periodic Boundary Solvated Molecular Dynamic Simulation of the Glucocorticoid Receptor Protein DNA Binding Domain in Complex with a Nucleosome DNA Model Containing Five Glucocorticoid Response Elements (GREs)
We investigated protein/DNA interactions, using Particle Mesh Ewald (PME) periodic boundary molecular dynamics simulations of a solvated dimer of the glucocorticoid receptor (GR) protein DNA binding domain (DBD) in complex with a mouse mammary tumor virus (MMTV) nucleosome model containing a glucocorticoid response element (GRE) DNA Sequence (Figure 1). We are using the NAMD program, which is described as "a parallel, object-oriented molecular dynamics code designed for high-performance simulation of large biomolecular systems. NAMD scales to hundreds of processors on high-end parallel platforms and tens of processors on commodity clusters using switched fast Ethernet." By using the PME method we were able to calculate long-range electrostatic interactions within the complex. Amino acids of the GR DBD DNA recognition helix 3 form both direct and water mediated hydrogen bonds at cognate codon-anticodon nucleotide base and backbone sites within the right and left DNA major groove half-sites and flanking regions of the GRE. Finally, structural changes in the MMTV nucleosome DNA as a result of protein binding are discussed. These findings offer a code for site specific DNA recognition by the GR protein based on stereo-chemical complementarity, electrostatic attraction and H-bonding between amino acid side chains within the protein?s DNA recognition helix and cognate codon-anticodon nucleotides within the GRE.
Figure 1:A computer model of glucocorticoid receptor (GR) protein DNA binding domain (DBD) in complex with a mouse mammary tumor virus (MMTV) nucleosome model containing a glucocorticoid response element (GRE) DNA Sequence. a) The model is shown in a 170 Angstrom cube of water molecules. This complex has 24,831 solute atoms, 445,986 water atoms and a total of 470,817 atoms. b) The complex is shown with the water molecules removed for visual clarity.
Lester F. Harris*
Hickok Memorial Cancer Research Laboratory