title: Focusing on shared subpockets - new developments in fragment-based drug discovery.
abstract: BACKGROUND
  Protein-protein interactions (PPIs) are important targets for understanding fundamental biology and for the development of therapeutic agents. Based on different physicochemical properties, numerous pieces of software (e.g., POCKETQUERY, ANCHORQUERY and FTMap) have been reported to find pockets on protein surfaces and have applications in facilitating the design and discovery of small-molecular-weight compounds that bind to these pockets.
  
  
  METHODS
  The authors discuss a pocket-centric method of analyzing PPI interfaces, which prioritize their pockets for small-molecule drug discovery and the importance of multicomponent reaction chemistry as starting points for undruggable targets. The authors also provide their perspectives on the field.
  
  
  CONCLUSIONS
  Only the tight interplay of efficient computational methods capable of screening a large chemical space and fast synthetic chemistry will lead to progress in the rational design of PPI antagonists in the future. Early drug discovery platforms will also benefit from efficient rapid feedback loops from early clinical research back to molecular design and the medicinal chemistry bench.
authors: a 1 University of Groningen, A. Deusinglaan, Department of Drug Design, 1, Groningen 9700 AD, The Netherlands a.s.s.domling@rug.nl.|b 2 Sohag University, Faculty of Science, Chemistry Department , Sohag 82524, Egypt.
authors: Eman M M
authors: EM
authors: Abdelraheem
authors: c 3 University of Pittsburgh, Department of Computational Biology, School of Medicine , 3501 Fifth Avenue, Suite 3064, Biomedical Science Tower 3 (BST3), Pittsburgh, PA 15260, USA.
authors: Carlos J
authors: CJ
authors: Camacho
authors: a 1 University of Groningen, A. Deusinglaan, Department of Drug Design, 1, Groningen 9700 AD, The Netherlands a.s.s.domling@rug.nl.|b 2 Sohag University, Faculty of Science, Chemistry Department , Sohag 82524, Egypt.
authors: Alexander
authors: A
authors: Dömling
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012984:Software
chemical_list: D011506:Proteins
keywords: ANCHORQUERY; Anchor; POCKETQUERY; chemical space; multicomponent reaction; pocket cluster; protein–protein interactions; virtual screening