  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)-g. 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.
