title: Allo-network drugs: extension of the allosteric drug concept to protein- protein interaction and signaling networks.
abstract: Allosteric drugs are usually more specific and have fewer side effects than orthosteric drugs targeting the same protein. Here, we overview the current knowledge on allosteric signal transmission from the network point of view, and show that most intra-protein conformational changes may be dynamically transmitted across protein-protein interaction and signaling networks of the cell. Allo-network drugs influence the pharmacological target protein indirectly using specific inter-protein network pathways. We show that allo-network drugs may have a higher efficiency to change the networks of human cells than those of other organisms, and can be designed to have specific effects on cells in a diseased state. Finally, we summarize possible methods to identify allo-network drug targets and sites, which may develop to a promising new area of systems-based drug design.
authors: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary. szia@enzim.hu
authors: András
authors: A
authors: Szilágyi
authors: Ruth
authors: R
authors: Nussinov
authors: Péter
authors: P
authors: Csermely
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D055808:Drug Discovery; D015507:Drugs, Investigational / Q000494:pharmacology*; D005057:Eukaryotic Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D011506:Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013816:Thermodynamics
chemical_list: D015507:Drugs, Investigational; D008024:Ligands; D011506:Proteins