title: Flexible receptor docking for drug discovery.
abstract: BACKGROUND
  Molecular docking has become a popular method for virtual screening. Docking small molecules to a rigid biological receptor is fast but could produce many false negatives and identify less diverse compounds. Flexible receptor docking has alleviated this problem.
  
  
  METHODS
  This article focuses on reviewing ensemble docking as an approximate but inexpensive method to incorporate receptor flexibility in molecular docking. It outlines key features and recent advances of this method and points out problem areas that need to be addressed to make it even more useful in drug discovery.
  
  
  CONCLUSIONS
  Among the different methods introduced for flexible receptor docking, ensemble docking represents one of the most popular approaches, especially for high-throughput virtual screening. One can generate structural ensembles by using experimental structures, by structural modeling and by various types of molecular simulations. In building a structural ensemble, a judicious choice of the structures to be included can improve performance. Furthermore, reducing the size of the structural ensemble can cut computational costs, and removing the structures that can bind few ligands well could enrich the number of true actives identified by ensemble docking. The ability of ensemble docking to identify more true positives at the top of a rank-ordered list also depends on the choice of the methods to score and rank compounds, an area that needs further research.
authors: a University of Missouri-St. Louis, Department of Chemistry and Biochemistry , 1 University Boulevard, St. Louis, MO 63121, USA +1 31 4516 5318 ; wongch@umsl.edu.
authors: Chung F
authors: CF
authors: Wong
mesh_terms: D003198:Computer Simulation; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation
chemical_list: D008024:Ligands
keywords: Boltzmann-enhanced discrimination of receiver operating characteristics; conformational transition path; enrichment factor; ensemble docking; molecular dynamics; normal mode; replica-exchange simulation; simulated annealing cycling