Towards drugs targeting multiple proteins in a systems biology approach

O. Keskin, A. Gursoy, Buyong Ma, Ruth Nussinov*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


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 protein-protein interaction target. The challenge we now face is how to pick the targets and how to improve the efficiency of designed partially-specific multi-target drugs that would block parallel pathways in the network.

Original languageEnglish
Pages (from-to)943-951
Number of pages9
JournalCurrent Topics in Medicinal Chemistry
Issue number10
StatePublished - May 2007


  • Allosteric site
  • Drug design
  • FK1012
  • G protein-coupled receptors
  • Hot regions


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