Dynamics-Driven Allostery in Protein Kinases

Trends Biochem Sci. 2015 Nov;40(11):628-647. doi: 10.1016/j.tibs.2015.09.002. Epub 2015 Oct 21.


Protein kinases have very dynamic structures and their functionality strongly depends on their dynamic state. Active kinases reveal a dynamic pattern with residues clustering into semirigid communities that move in μs-ms timescale. Previously detected hydrophobic spines serve as connectors between communities. Communities do not follow the traditional subdomain structure of the kinase core or its secondary structure elements. Instead they are organized around main functional units. Integration of the communities depends on the assembly of the hydrophobic spine and phosphorylation of the activation loop. Single mutations can significantly disrupt the dynamic infrastructure and thereby interfere with long-distance allosteric signaling that propagates throughout the whole molecule. Dynamics is proposed to be the underlying mechanism for allosteric regulation in protein kinases.

Keywords: allostery; community analysis; protein dynamics; protein kinases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allosteric Regulation
  • Hydrophobic and Hydrophilic Interactions
  • Phosphorylation
  • Protein Kinases / metabolism*


  • Protein Kinases