Andras Szilagyi, Ruth Nussinov and Peter Csermely Pages 64 - 77 ( 14 )
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.
Allo-network drugs, allosteric drugs, interactome, protein-protein interaction networks, protein structure networks, signaling networks
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Karolina ut 29, H-1113 Budapest, Hungary.