Small molecules, big targets: drug discovery faces the protein–protein interaction challenge
Author:
Publisher
Springer Science and Business Media LLC
Subject
Drug Discovery,Pharmacology,General Medicine
Link
http://www.nature.com/articles/nrd.2016.29.pdf
Reference168 articles.
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3. Clackson, T. & Wells, J. A. A hot spot of binding energy in a hormone–receptor interface. Science 267, 383–386 (1995). A seminal paper presenting the crystal structure of human growth hormone and a domain of its receptor and systematically mutating interface residues to Ala.
4. Bogan, A. A. & Thorn, K. S. Anatomy of hot spots in protein interfaces. J. Mol. Biol. 280, 1–9 (1998). This paper examines the residue composition of hot spots at PPI interfaces, demonstrating an enrichment for certain amino acids. The importance of solvent occlusion around hot spot residues is also discussed.
5. Smith, M. C. & Gestwicki, J. E. Features of protein–protein interactions that translate into potent inhibitors: topology, surface area and affinity. Expert Rev. Mol. Med. 14, e16 (2012).
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