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De Novo Drug Design

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Chemoinformatics and Computational Chemical Biology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 672))

Abstract

Computer-assisted molecular design supports drug discovery by suggesting novel chemotypes and compound modifications for lead structure optimization. While the aspect of synthetic feasibility of the automatically designed compounds has been neglected for a long time, we are currently witnessing an increased interest in this topic. Here, we review state-of-the-art software for de novo drug design with a special emphasis on fragment-based techniques that generate druglike, synthetically accessible compounds. The importance of scoring functions that can be used to predict compound reactivity and potency is highlighted, and several promising solutions are discussed. Recent practical validation studies are presented that have already demonstrated that rule-based fragment assembly can result in novel synthesizable compounds with druglike properties and a desired biological activity.

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Acknowledgments

The authors thank Herbert Köppen and Karl-Heinz Baringhaus for stimulating discussion. M.H. is grateful to Merz Pharmaceuticals for a scholarship. This research was supported by the Beilstein Institut zur Förderung der Chemischen Wissenschaften and the DFG (SFB579, project A11.2).

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Authors and Affiliations

  1. Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe University, Frankfurt, Germany

    Markus Hartenfeller & Gisbert Schneider

  2. Institute of Pharmaceutical Sciences, Eidgenössische Technische Hochschule (ETH), Zürich, Switzerland

    Gisbert Schneider

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  1. Markus Hartenfeller
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  1. , Department of Life Science Informatics, Rheinische Friedrich-Wilhelms-Universitä, Dahlmannstr. 2, Bonn, 53113, Germany

    Jürgen Bajorath

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Hartenfeller, M., Schneider, G. (2010). De Novo Drug Design. In: Bajorath, J. (eds) Chemoinformatics and Computational Chemical Biology. Methods in Molecular Biology, vol 672. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-839-3_12

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  • DOI: https://doi.org/10.1007/978-1-60761-839-3_12

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