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Structure-Based Target Druggability Assessment

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Target Identification and Validation in Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 986))

Abstract

The focus of this chapter is on the important concepts behind the in silico techniques that are used today to assess target druggability. The first step of the assessment consists of finding cavity space in the protein using 2D and/or 3D topological concepts. These concepts underlie the geometry and energy-based pocketfinder algorithms. Analysis pursues on the physico-chemical complementarity between the binding site and the drug like molecule. Geometrical and molecular flexibility aspect are also included in this assessment. The presence of hot interaction spots are shown to be particularly important for targeting protein-protein interactions. Finally, binding site promiscuity can be assessed by large scale structural comparison with other targets. Common chemical features amongst protein cavities can predict potential cross-reactivity with unwanted targets.

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Acknowledgment

The author thanks Dr. Fabrice Moriaud for providing picture 5 on the MedSuMo software.

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Trosset, JY., Vodovar, N. (2013). Structure-Based Target Druggability Assessment. In: Moll, J., Colombo, R. (eds) Target Identification and Validation in Drug Discovery. Methods in Molecular Biology, vol 986. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-311-4_10

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  • DOI: https://doi.org/10.1007/978-1-62703-311-4_10

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