Induced fit in liver X receptor beta: a molecular dynamics-based investigation

Proteins. 2008 Aug 15;72(3):873-82. doi: 10.1002/prot.21977.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Crystallography, X-Ray
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism*
  • Ligands
  • Liver X Receptors
  • Models, Molecular*
  • Orphan Nuclear Receptors
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protons
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • DNA-Binding Proteins
  • Ligands
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Protons
  • Receptors, Cytoplasmic and Nuclear