In Silico Adoption of an Orphan Nuclear Receptor NR4A1

PLoS One. 2015 Aug 13;10(8):e0135246. doi: 10.1371/journal.pone.0135246. eCollection 2015.

Abstract

A 4.1 μs molecular dynamics simulation of the NR4A1 (hNur77) apo-protein has been undertaken and a previously undetected druggable pocket has become apparent that is located remotely from the 'traditional' nuclear receptor ligand-binding site. A NR4A1/bis-indole ligand complex at this novel site has been found to be stable over 1 μs of simulation and to result in an interesting conformational transmission to a remote loop that has the capacity to communicate with a NBRE within a RXR-α/NR4A1 heterodimer. Several features of the simulations undertaken indicate how NR4A1 can be affected by alternate-site modulators.

MeSH terms

  • Binding Sites
  • Computer Simulation
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / chemistry*
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism*
  • Protein Binding
  • Protein Structure, Secondary
  • Retinoid X Receptor alpha / metabolism*

Substances

  • Ligands
  • NR4A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Retinoid X Receptor alpha

Grants and funding

The authors have no support or funding to report.