Unbinding of Retinoic Acid from its Receptor Studied by Steered Molecular Dynamics
Dorina Kosztin, Sergei Izrailev, Klaus Schulten
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)-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.
Create a lesson
Related papers
A Variational Framework for Nonlinear Chemical Thermodynamics Employing the Maximum Energy Dissipation Principle
Adam Moroz
Retrievable but Unencountered: The Missing Exposure Denominator in Large Academic Ebook Collections
Jette Veenstra, Mauricio Munoz Arias
Where Energy Is Spent Sets the Depth of Kinetic Proofreading
Uğur Çetiner
On the Role of Dispersion in One Model of Propagation of Elastic Excitations in Nerves
Alexander I. Kozlov
Quantifying the Biophysical Properties of Red Blood Cells in Gaucher Disease
Zhaojie Chai, Marine de Person, Pierre A. Buffet et al.
Roles of vortices and turbulent eddies in particle preferential concentration and deposition in the human respiratory tract
Mengtao Li, Yawei Wang, Wentao Feng et al.