Multipose binding in molecular docking

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung



Molecular docking has been extensively applied in virtual screening of small molecule libraries for lead identification and optimization. A necessary prerequisite for successful differentiation between active and non-active ligands is the accurate prediction of their binding affinities in the complex by use of docking scoring functions. However, many studies have shown rather poor correlations between docking scores and experimental binding affinities. Our work aimed to improve this correlation by implementing a multipose binding concept in the docking scoring scheme. Multipose binding, i.e., the property of certain protein-ligand complexes to exhibit different ligand binding modes, has been shown to occur in nature for a variety of molecules. We conducted a high-throughput docking study and implemented multipose binding in the scoring procedure by considering multiple docking solutions in binding affinity prediction. In general, improvement of the agreement between docking scores and experimental data was observed, and this was most pronounced in complexes with large and flexible ligands and high binding affinities. Further developments of the selection criteria for docking solutions for each individual complex are still necessary for a general utilization of the multipose binding concept for accurate binding affinity prediction by molecular docking.


Seiten (von - bis)2622-45
FachzeitschriftInternational journal of molecular sciences
PublikationsstatusVeröffentlicht - 14 Feb. 2014

Externe IDs

PubMedCentral PMC3958872
Scopus 84893978461


Ziele für nachhaltige Entwicklung


  • HIV Protease/chemistry, HIV Protease Inhibitors/chemistry, Ligands, Molecular Docking Simulation, Peptides/chemistry, Principal Component Analysis, Protein Binding, Proteins/chemistry, Small Molecule Libraries/chemistry, Software, src Homology Domains