A Hybrid Virtual Screening Protocol Based on Binding Mode Similarity

  • Andrew Anighoro
  • Jürgen BajorathEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1824)


In structure-based virtual screening (SBVS), a scoring function is usually applied to rank a database of docked compounds. Docking programs are often successful in reproducing experimental binding modes; however, the estimation of binding affinity still is the Achilles’ heel of docking. The integration of SB and ligand-based (LB) methods is considered a promising strategy to increase hit rates in VS. Herein, we describe a hybrid protocol that is based on the assessment of binding mode similarity between docked compounds and a bound reference ligand. In this context, both experimental and computationally modeled poses have been successfully used as references for three-dimensional (3D) similarity calculations. In this chapter, the methods applied in recent validation studies are described.

Key words

Virtual screening Compound ranking Molecular docking Binding mode 3D similarity Protein–ligand interaction fingerprints Homology modeling 



We thank OpenEye Scientific Software, Inc., for a free academic license of the OpenEye Toolkit and Chemical Computing Group, Inc., for academic teaching licenses of the Molecular Operating Environment.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal ChemistryRheinische Friedrich-Wilhelms-UniversitätBonnGermany

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