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In Silico Target Druggability Assessment: From Structural to Systemic Approaches

  • Jean-Yves TrossetEmail author
  • Christian Cavé
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1953)

Abstract

This chapter will focus on today’s in silico direct and indirect approaches to assess therapeutic target druggability. The direct approach tries to infer from the 3D structure the capacity of the target protein to bind small molecule in order to modulate its biological function. Algorithms to recognize and characterize the quality of the ligand interaction sites whether within buried protein cavities or within large protein-protein interface will be reviewed in the first part of the paper. In the case a ligand-binding site is already identified, indirect aspects of target druggability can be assessed. These indirect approaches focus first on target promiscuity and the potential difficulties in developing specific drugs. It is based on large-scale comparison of protein-binding sites. The second aspect concerns the capacity of the target to induce resistant pathway once it is inhibited or activated by a drug. The emergence of drug-resistant pathways can be assessed through systemic analysis of biological networks implementing metabolism and/or cell regulation signaling.

Key words

Drug targets Hot spots Druggability Flo-QXP Pocket finder Structure superimposition Target promiscuity Protein cavity 

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Bioinformation Research Laboratory, Sup’BiotechVillejuifFrance
  2. 2.BioCIS UFR Pharmacie UMR CNRS 8076Université Paris SaclayOrsayFrance

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