Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain in complex with DNA and free in solution

Biophys J. 1995 Feb;68(2):402-26. doi: 10.1016/S0006-3495(95)80203-1.

Abstract

Molecular dynamics simulations have been performed on the glucocorticoid receptor DNA binding domain (GR DBD) in aqueous solution as a dimer in complex with DNA and as a free monomer. In the simulated complex, we find a slightly increased bending of the DNA helix axis compared with the crystal structure in the spacer region of DNA between the two half-sites that are recognized by GR DBD. The bend is mainly caused by an increased number of interactions between DNA and the N-terminal extended region of the sequence specifically bound monomer. The recognition helices of GR DBD are pulled further into the DNA major groove leading to a weakening of the intrahelical hydrogen bonds in the middle of the helices. Many ordered water molecules with long residence times are found at the intermolecular interfaces of the complex. The hydrogen-bonding networks (including water bridges) on either side of the DNA major groove involve residues that are highly conserved within the family of nuclear receptors. Very similar hydrogen-bonding networks are found in the estrogen receptor (ER) DBD in complex with DNA, which suggests that this is a common feature for proper positioning of the recognition helix in ER DBD and GR DBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Computer Simulation
  • DNA / chemistry*
  • DNA / ultrastructure
  • DNA-Binding Proteins / chemistry*
  • Diffusion
  • Hydrogen Bonding
  • Metalloproteins / chemistry
  • Models, Molecular
  • Molecular Sequence Data
  • Movement
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Receptors, Glucocorticoid / chemistry*
  • Solutions
  • Solvents
  • Surface Properties
  • Water / chemistry

Substances

  • DNA-Binding Proteins
  • Metalloproteins
  • Receptors, Glucocorticoid
  • Solutions
  • Solvents
  • Water
  • DNA