Network-Based Strategies Can Help Mono- and Poly-pharmacology Drug Discovery: A Systems Biology View
H. Billur Engin, Attila Gursoy, Ruth Nussinov and Ozlem Keskin
Affiliation: Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Rumelifeneri Yolu, 34450 Sariyer Istanbul, Turkey.
Keywords: Poly-pharmacology, network pharmacology, protein-protein interaction inhibitors, systems biology, protein-protein interfaces,
The cellular network and its environment govern cell and organism behavior and are fundamental to the comprehension of
function, misfunction and drug discovery. Over the last few years, drugs were observed to often bind to more than one target; thus, polypharmacology
approaches can be advantageous, complementing the “one drug - one target” strategy. Targeting drug discovery from the
systems biology standpoint can help in studies of network effects of mono- and poly-pharmacology. In this mini-review, we provide an
overview of the usefulness of network description and tools for mono- and poly-pharmacology, and the ways through which protein interactions
can help single- and multi-target drug discovery efforts. We further describe how, when combined with experimental data,
modeled structural networks which can predict which proteins interact and provide the structures of their interfaces, can model the cellular
pathways, and suggest which specific pathways are likely to be affected. Such structural networks may facilitate structure-based drug
design; forecast side effects of drugs; and suggest how the effects of drug binding can propagate in multi-molecular complexes and pathways.
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