Advanced Methods for Accessing Protein Shape-Shifting Present New Therapeutic Opportunities

Catherine R. Knoverek, Gaya K. Amarasinghe, Gregory R. Bowman

Research output: Contribution to journalReview article

4 Scopus citations

Abstract

A protein is a dynamic shape-shifter whose function is determined by the set of structures it adopts. Unfortunately, atomically detailed structures are only available for a few conformations of any given protein, and these structures have limited explanatory and predictive power. Here, we provide a brief historical perspective on protein dynamics and introduce recent advances in computational and experimental methods that are providing unprecedented access to protein shape-shifting. Next, we focus on how these tools are revealing the mechanism of allosteric communication and features like cryptic pockets; both of which present new therapeutic opportunities. A major theme is the importance of considering the relative probabilities of different structures and the control one can exert over protein function by modulating this balance.

Original languageEnglish
Pages (from-to)351-364
Number of pages14
JournalTrends in biochemical sciences
Volume44
Issue number4
DOIs
StatePublished - Apr 2019

Keywords

  • allostery
  • cryptic pockets
  • protein dynamics

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