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

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.

SUBMITTER: Knoverek CR

PROVIDER: S-EPMC6422738 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Knoverek Catherine R CR Amarasinghe Gaya K GK Bowman Gregory R GR

Trends in biochemical sciences 20181214 4

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 foc ...[more]

PMID: 30555007

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