Format

Send to

Choose Destination
Trends Biochem Sci. 2018 Dec 13. pii: S0968-0004(18)30248-2. doi: 10.1016/j.tibs.2018.11.007. [Epub ahead of print]

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

Author information

1
Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
2
Department of Pathology & Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
3
Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. Electronic address: g.bowman@wustl.edu.

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.

KEYWORDS:

allostery; cryptic pockets; protein dynamics

PMID:
30555007
DOI:
10.1016/j.tibs.2018.11.007

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center