A comparison between enrichment optimization algorithm (EOA)-based and docking-based virtual screening

Jacob Spiegel, Hanoch Senderowitz

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Virtual screening (VS) is a well-established method in the initial stages of many drug and material design projects. VS is typically performed using structure-based approaches such as molecular docking, or various ligand-based approaches. Most docking tools were designed to be as global as possible, and consequently only require knowledge on the 3D structure of the biotarget. In contrast, many ligand-based approaches (e.g., 3D-QSAR and pharmacophore) require prior development of project-specific predictive models. Depending on the type of model (e.g., classification or regression), predictive ability is typically evaluated using metrics of performance on either the training set (e. g., Q2 cv) or the test set (e.g., specificity, selectivity or Q2 F1/F2/F3). However, none of these metrics were developed with VS in mind, and consequently, their ability to reliably assess the performances of a model in the context of VS is at best limited. With this in mind we have recently reported the development of the enrichment optimization algorithm (EOA). EOA derives QSAR models in the form of multiple linear regression (MLR) equations for VS by optimizing an enrichment- based metric in the space of the descriptors. Here we present an improved version of the algorithm which better handles active compounds and which also takes into account information on inactive (either known inactive or decoy) compounds. We compared the improved EOA in smallscale VS experiments with three common docking tools, namely, Glide-SP, GOLD and AutoDock Vina, employing five molecular targets (acetylcholinesterase, human immunodeficiency virus type 1 protease, MAP kinase p38 alpha, urokinase-type plasminogen activator, and trypsin I). We found that EOA consistently outperformed all docking tools in terms of the area under the ROC curve (AUC) and EF1% metrics that measured the overall and initial success of the VS process, respectively. This was the case when the docking metrics were calculated based on a consensus approach and when they were calculated based on two different sets of single crystal structures. Finally, we propose that EOA could be combined with molecular docking to derive target-specific scoring functions.

Original languageEnglish
Article number43
JournalInternational Journal of Molecular Sciences
Issue number1
StatePublished - 1 Jan 2022

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • AutoDock Vina
  • Docking
  • Enrichment optimization algorithm
  • GOLD
  • Glide
  • QSAR
  • Virtual screening


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