Druggable pockets and binding site centric chemical space: a paradigm shift in drug discovery.
Detection, comparison and analyses of binding pockets are pivotal to structure-based drug design endeavors, from hit identification, screening of exosites and de-orphanization of protein functions to the anticipation of specific and non-specific binding to off- and anti-targets. Here, we analyze protein-ligand complexes and discuss methods that assist binding site identification, prediction of druggability and binding site comparison. The full potential of pockets is yet to be harnessed, and we envision that better understanding of the pocket space will have far-reaching implications in the field of drug discovery, such as the design of pocket-specific compound libraries and scoring functions.
Pérot
Stéphanie
S
Université Paris Diderot, 75013 Paris, France.
Sperandio
Olivier
O
Miteva
Maria A
MA
Camproux
Anne-Claude
AC
Villoutreix
Bruno O
BO
D001665:Binding Sites; D016503:Drug Delivery Systems; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D008024:Ligands; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D054852:Small Molecule Libraries / Q000737:chemistry
D008024:Ligands; D004364:Pharmaceutical Preparations; D054852:Small Molecule Libraries