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PMID: 7696496 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Biophysical journal ·Vol. 68 ·No. 2 ·1995-02-00 ·Pages 402-26

Eriksson MA, Härd T, Nilsson L

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.

MeSH Terms
Amino Acid Sequence Base Sequence Binding Sites Computer Simulation DNA/chemistry,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
Chemicals
DNA-Binding Proteins Metalloproteins Receptors, Glucocorticoid Solutions Solvents Water DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Eriksson M A
Karolinska Institute Center for Structural Biochemistry, NOVUM, Huddinge, Sweden.
Härd T
Nilsson L
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1016/S0006-3495(95)80203-1
Published
1995-02-00
Pages
402-26
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1281706
Subset
IM
External Links
PubMed source DOI: 10.1016/S0006-3495(95)80203-1 PMC Full Text View journal details
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