Towards Drugs Targeting Multiple Proteins in a Systems Biology Approach

Author(s): O. Keskin , A. Gursoy , B. Ma , R. Nussinov .

Journal Name: Current Topics in Medicinal Chemistry

Volume 7 , Issue 10 , 2007

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Protein-protein interactions are increasingly becoming drug targets. This is understandable, since they are crucial at all levels of cellular expression and growth. In practice, targeting specific disease-related interactions has proven difficult, with success varying with specific complexes. Here, we take a Systems Biology approach to targeting protein-protein interactions. Below, we first briefly review drug discovery targeted at protein-protein interactions; we classify protein-protein complexes with respect to their types of interactions and their roles in cellular function and as being targets in drug design; we describe the properties of the interfaces as related to drug design, focusing on hot spots and surface cavities; and finally, in particular, we cast the interactions into the cellular network system, highlighting the challenge of partially targeting multiple interactions in the networks as compared to hitting a specific proteinprotein interaction target. The challenge we now face is how to pick the targets and how to improve the efficiency of designed partiallyspecific multi-target drugs that would block parallel pathways in the network.

Keywords: hot regions, Drug Design, allosteric site, G protein-coupled receptors, FK1012

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Article Details

Year: 2007
Page: [943 - 951]
Pages: 9
DOI: 10.2174/156802607780906690
Price: $58

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