Beware of docking!

•Docking is a fast and low-cost technology for large-scale drug screening. •Molecular dynamics simulations sometimes reveal docking poses that are actually unstable. •Drug design should consider both binding affinity and residence time. •A molecular dynamics simulation is currently not long enough to accurately model residence time. Docking is now routine in virtual screening or lead optimization for drug screening and design. The number of papers related to docking has dramatically increased over the past decade. However, there are many issues to consider when undertaking a docking study. Frequent problems or issues arise, such as the wrong binding site of the target protein, screening using an unsuitable small-molecule database, the choice of docking pose, high dock score but failed in molecular dynamics (MD) simulation, and lack of clarity over whether the compound is an inhibitor or agonist. These problems should be cause for caution and concern before performing docking. Some papers show comprehensive biochemistry experiments but only a simple docking figure. This review presents some evidence to show that the docking might be questionable, despite a high score. In some cases, the accuracy of docking can even change from 0% to 92.66%. Thus, please beware of docking! Docking is now routine in virtual screening or lead optimization for drug screening and design. The number of papers related to docking has dramatically increased over the past decade. However, there are many issues to consider when undertaking a docking study. Frequent problems or issues arise, such as the wrong binding site of the target protein, screening using an unsuitable small-molecule database, the choice of docking pose, high dock score but failed in molecular dynamics (MD) simulation, and lack of clarity over whether the compound is an inhibitor or agonist. These problems should be cause for caution and concern before performing docking. Some papers show comprehensive biochemistry experiments but only a simple docking figure. This review presents some evidence to show that the docking might be questionable, despite a high score. In some cases, the accuracy of docking can even change from 0% to 92.66%. Thus, please beware of docking! Erratum: Beware of Docking!Yu-Chian ChenTrends in Pharmacological SciencesFebruary 20, 2015In BriefIn the article by Yu-Chian Chen ‘Beware of Docking!’, which is published in this issue of Trends in Pharmacological Sciences, there was an error in an earlier online version of the manuscript. The original online publication did not make clear that Table 1 is extracted and reproduced from the website Click2Drug.org of the SIB Swiss Institute of Bioinformatics. For complete information, please refer to the original website, Click2Drug.org. Table 1 is reproduced in this article with permission. The author and Trends in Pharmacological Sciences apologize for the initial error. Full-Text PDF