Protein Engineering by Combined Computational and In Vitro Evolution Approaches

Lior Rosenfeld, Michael Heyne, Julia M. Shifman*, Niv Papo

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations


Two alternative strategies are commonly used to study protein-protein interactions (PPIs) and to engineer protein-based inhibitors. In one approach, binders are selected experimentally from combinatorial libraries of protein mutants that are displayed on a cell surface. In the other approach, computational modeling is used to explore an astronomically large number of protein sequences to select a small number of sequences for experimental testing. While both approaches have some limitations, their combination produces superior results in various protein engineering applications. Such applications include the design of novel binders and inhibitors, the enhancement of affinity and specificity, and the mapping of binding epitopes. The combination of these approaches also aids in the understanding of the specificity profiles of various PPIs.

Original languageAmerican English
Pages (from-to)421-433
Number of pages13
JournalTrends in Biochemical Sciences
Issue number5
StatePublished - 1 May 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd.


  • Binding affinity
  • Combinatorial selection
  • Computational protein design
  • Novel binding domains
  • Protein engineering
  • Protein-protein interactions


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