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Docking & Scoring
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InterAction Meeting Session, Bryn Mawr, Philadelphia, USA
Tuesday 14 October 2008
chaired by Chaya Duraiswami (GlaxoSmithKline) Bio....
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A recent publication has highlighted some of the limitations in the ability of commercially available docking programs to predict ligand binding affinities correctly (1). These authors summarize that while docking programs can generate ligand poses similar to crystallographically determined protein/ligand complex structures for some targets, no single program usually does well on all targets. Additionally, scoring functions are usually not successful at distinguishing the crystallographic conformation from the set of docked poses. Lastly, while docking programs can identify active compounds from a pharmaceutically relevant pool of decoy compounds, no single program has performed well on all the targets. These limitations undermine the credibility of docking programs as a virtual-screening tool.
This “docking and scoring” session highlights some advances made to this field to address the limitations stated above. Professor John Irwin, will address the necessity of utilizing appropriate experimental design principles while conducting both retrospective and prospective docking studies and analyzing their results. The talk by Georgia McGaughey compares the utility of docking studies with other ligand-based approaches. This should help us understand when docking might be a worthwhile virtual-screening tool to consider and when other methods might be more appropriate; and if it is important for the docking program to generate ligand conformations similar to crystallographically determined protein/ligand complex structures while conducting a virtual screening exercise. Johannes Voigt will present an application of cross docking with CDK2 inhibitors as the test case, to determine if one is obtaining the right answers for the right reasons, as opposed to a chance correlation. Talks by Lance Westerhoff and Zsolt Zsoldos will highlight some advances made in the area of scoring functions to correctly predict binding affinity and rank order ligands by their relative potency.
Reference
(1) A Critical Assessment of Docking Programs and Scoring Functions; Gregory L Warren, et. al J. Med. Chem., 49 (20), 5912 -5931, 2006
Presenters & Discussions Leaders
John Irwin (UCSF), Retrospective and Prospective Investigation of Docking Performance Abstract & Bio....
Georgia McGaughey (Merck), Ligand- and Structure-based methods: Comparison of Methods Abstract & Bio....
Johannes H. Voigt (Schering Plough), Cross-docking to CDK2: a Virtual Screening Study Abstract & Bio....
Lance Westerhoff (Quantum Bio), Application of Quantum Mechanical Pairwise Energy Decomposition to Structure-based Drug Design Abstract & Bio....
Zsolt Zsoldos (SimBioSys Inc.), The eHiTS Scoring Function
Abstract & Bio....
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