Employing directed evolution for the functional analysis of multi-specific proteins

Maxim Levin, Dotan Amar, Amir Aharoni

Research output: Contribution to journalArticlepeer-review


Multi-specific proteins located at the heart of complex protein-protein interaction (PPI) networks play essential roles in the survival and fitness of the cell. In addition, multi-specific or promiscuous enzymes exhibit activity toward a wide range of substrates so as to increase cell evolvability and robustness. However, despite their high importance, investigating the in vivo function of these proteins is difficult, due to their complex nature. Typically, deletion of these proteins leads to the abolishment of large PPI networks, highlighting the difficulty in examining the contributions of specific interactions/activities to complex biological processes and cell phenotypes. Protein engineering approaches, including directed evolution and computational protein design, allow for the generation of multi-specific proteins in which certain activities remain intact while others are abolished. The generation and examination of these mutants both in vitro and in vivo can provide high-resolution analysis of biological processes and cell phenotypes and provide new insight into the evolution and molecular function of this important protein family.

Original languageAmerican English
Pages (from-to)3511-3516
Number of pages6
JournalBioorganic and Medicinal Chemistry
Issue number12
StatePublished - 15 Jun 2013


  • Directed evolution
  • Multi-specific proteins
  • Protein-networks

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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