Wednesday, October 3, 2012

1210.0330 (Peter Csermely et al.)

Structure and dynamics of molecular networks: A novel paradigm of drug
discovery. A comprehensive review
   [PDF]

Peter Csermely, Tamas Korcsmaros, Huba J. M. Kiss, Gabor London, Ruth Nussinov
Despite considerable progress in genome- and proteome-based high-throughput screening methods and in rational drug design, the increase in approved drugs in the past decade did not match the increase of drug development costs. The network approach not only gives a systems-level understanding of drug action and disease complexity, but can also help to improve the efficiency of drug design. Here we give a comprehensive assessment of the analytical tools of network topology and dynamics. We summarize the current knowledge and the state-of-the-art use of chemical similarity, protein structure, protein-protein interaction, signaling, genetic interaction and metabolic networks in the discovery of drug targets. We show how network techniques can help in the identification of single-target, edgetic, multi-target and allo-network drug target candidates. We review the recent boom in network methods helping hit identification, lead selection optimizing drug efficacy, as well as minimizing side-effects and drug toxicity. Successful network-based drug development strategies are shown through the examples of infections, cancer, metabolic diseases, neurodegenerative diseases and aging. Finally, summarizing more than 1100 cited references we suggest an optimized protocol of network-aided drug development, and provide a list of systems-level hallmarks of drug quality. Finally, we highlight network-related drug development trends both at protein structure and cellular levels helping to achieve these hallmarks by a cohesive, global approach.
View original: http://arxiv.org/abs/1210.0330

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