title: Induced fit in liver X receptor beta: a molecular dynamics-based investigation.
abstract: Ligand induced fit phenomenon occurring at the ligand binding domain of the liver X receptor beta (LXRbeta) was investigated by means of molecular dynamics. Reliability of a 4-ns trajectory was tested from two distinct LXRbeta crystal complexes 1PQ6B/GW and 1PQ9B/T09 characterized by an open and a closed state of the pocket, respectively. Crossed complexes 1PQ6B/T09 and 1PQ9B/GW were then submitted to the same molecular dynamic conditions, which were able to recover LXRbeta conformations similar to the original crystallography data. Analysis of "open to closed" and "closed to open" conformational transitions pointed out the dynamic role of critical residues lining the ligand binding pocket involved in the local remodeling upon ligand binding (e.g., Phe271, Phe329, Phe340, Arg319, Glu281). Altogether, the present study indicates that the molecular dynamic protocol is a consistent approach for managing LXRbeta-related induced fit process. This protocol could therefore be used for refining ligand docking solutions of a structure-based design strategy.
authors.affiliation: Nancy-Université, Groupe ORPAILLEUR, UMR CNRS/UHP 7503, LORIA, Campus Scientifique, BP239, 54506 Vandoeuvre-lès-Nancy Cedex, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Beautrait
authors.forename: Arnaud S
authors.initials: AS
authors.lastname: Karaboga
authors.forename: Michel
authors.initials: M
authors.lastname: Souchet
authors.forename: Bernard
authors.initials: B
authors.lastname: Maigret
mesh_terms: D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D000071518:Liver X Receptors; D008958:Models, Molecular; D057093:Orphan Nuclear Receptors; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011522:Protons; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011522:Protons; D018160:Receptors, Cytoplasmic and Nuclear