Format

Send to

Choose Destination
Biophys J. 1999 Jan;76(1 Pt 1):188-97.

Unbinding of retinoic acid from its receptor studied by steered molecular dynamics.

Author information

1
Departments of Chemistry and Physics, Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 USA.

Abstract

Retinoic acid receptor (RAR) is a ligand-dependent transcription factor that regulates the expression of genes involved in cell growth, differentiation, and development. Binding of the retinoic acid hormone to RAR is accompanied by conformational changes in the protein which induce transactivation or transrepression of the target genes. In this paper we present a study of the hormone binding/unbinding process in order to clarify the role of some of the amino acid contacts and identify possible pathways of the all-trans retinoic acid binding/unbinding to/from human retinoic acid receptor (hRAR)-gamma. Three possible pathways were explored using steered molecular dynamics simulations. Unbinding was induced on a time scale of 1 ns by applying external forces to the hormone. The simulations suggest that the hormone may employ one pathway for binding and an alternative "back door" pathway for unbinding.

PMID:
9876133
PMCID:
PMC1302510
DOI:
10.1016/S0006-3495(99)77188-2
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center