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Binding site characteristics in structure-based virtual screening: evaluation of current docking tools

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Abstract

Two new docking programs FRED (OpenEye Scientific Software) and Glide (Schrödinger, Inc.) in combination with various scoring functions implemented in these programs have been evaluated against a variety of seven protein targets (cyclooxygenase-2, estrogen receptor, p38 MAP kinase, gyrase B, thrombin, gelatinase A, neuraminidase) in order to assess their accuracy in virtual screening. Sets of known inhibitors were added to and ranked relative to a random library of drug-like compounds. Performance was compared in terms of enrichment factors and CPU time consumption. Results and specific features of the two new tools are discussed and compared to previously published results using FlexX (Tripos, Inc.) as a docking engine. In addition, general criteria for the selection of docking algorithms and scoring functions based on binding-site characteristics of specific protein targets are proposed.

Figure Enrichment factors obtained with FlexX, Glide and FRED docking engines in combination with different scoring functions for seven selected targets with highly variable binding sites

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Acknowledgements

The authors thank Tom Halgren from Schrödinger Inc. for providing Glide evaluation licenses and many discussions about this software, Jörg Weiser and Gerd Räther from Anterio Consult & Research for support, Anthony Nicholls, Matt Stahl and Mark McGann from OpenEye Software for providing FRED and OMEGA evaluation licenses and the implementation of ScreenScore into FRED. Matthias Rarey is thanked for his continuing support of FlexX and many fruitful discussions. We thank our colleagues at Roche Basel and in the Roche biostructure community for supporting our work.

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  1. Pharmaceuticals Division, Molecular Design, F. Hoffmann-La Roche Ltd, 4070, Basel, Switzerland

    Tanja Schulz-Gasch & Martin Stahl

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  1. Tanja Schulz-Gasch
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  2. Martin Stahl
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Correspondence to Tanja Schulz-Gasch.

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Schulz-Gasch, T., Stahl, M. Binding site characteristics in structure-based virtual screening: evaluation of current docking tools. J Mol Model 9, 47–57 (2003). https://doi.org/10.1007/s00894-002-0112-y

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