Cold Spots in Protein Binding

Jason Shirian, Oz Sharabi, Julia M. Shifman*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

20 Scopus citations

Abstract

Understanding the energetics and architecture of protein-binding interfaces is important for basic research and could potentially facilitate the design of novel binding domains for biotechnological applications. It is well accepted that a few key residues at binding interfaces (binding hot spots) are responsible for contributing most to the free energy of binding. In this opinion article, we introduce a new concept of ‘binding cold spots’, or interface positions occupied by suboptimal amino acids. Such positions exhibit a potential for affinity enhancement through various mutations. We give several examples of cold spots from different protein-engineering studies and argue that identification of such positions is crucial for studies of protein evolution and protein design.

Original languageAmerican English
Pages (from-to)739-745
Number of pages7
JournalTrends in Biochemical Sciences
Volume41
Issue number9
DOIs
StatePublished - 1 Sep 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd

Keywords

  • binding affinity
  • binding energetics
  • binding landscapes
  • protein–protein interactions
  • saturation mutagenesis

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