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.
Keywords: Allo-network drugs, allosteric drugs, interactome, protein-protein interaction networks, protein structure networks, signaling networks
Current Topics in Medicinal Chemistry
Title:Allo-Network Drugs: Extension of the Allosteric Drug Concept to Protein- Protein Interaction and Signaling Networks
Volume: 13 Issue: 1
Author(s): Andras Szilagyi, Ruth Nussinov and Peter Csermely
Affiliation:
Keywords: Allo-network drugs, allosteric drugs, interactome, protein-protein interaction networks, protein structure networks, 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.
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Szilagyi Andras, Nussinov Ruth and Csermely Peter, Allo-Network Drugs: Extension of the Allosteric Drug Concept to Protein- Protein Interaction and Signaling Networks, Current Topics in Medicinal Chemistry 2013; 13 (1) . https://dx.doi.org/10.2174/1568026611313010007
DOI https://dx.doi.org/10.2174/1568026611313010007 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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