Allostery in Its Many Disguises: From Theory to Applications

Structure. 2019 Apr 2;27(4):566-578. doi: 10.1016/j.str.2019.01.003. Epub 2019 Feb 7.

Abstract

Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop is used here to provide an overview of the progress and remaining limitations in the understanding of the mechanistic foundations of allostery gained from computational and experimental analyses of real protein systems and model systems. The main conceptual frameworks instrumental in driving the field are discussed. We illustrate the role of these frameworks in illuminating molecular mechanisms and explaining cellular processes, and describe some of their promising practical applications in engineering molecular sensors and informing drug design efforts.

Keywords: Allostery; allosteric drugs; allosteric material; allosteric switches; elastic network models; energy landscape; molecular dynamics; protein conformational changes; protein function; regulation; signal transduction.

Publication types

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

MeSH terms

  • Allosteric Regulation
  • Allosteric Site*
  • Animals
  • Biosensing Techniques*
  • Drug Design*
  • Gene Expression Regulation
  • Humans
  • Metabolic Networks and Pathways
  • Molecular Dynamics Simulation
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism
  • Signal Transduction
  • Thermodynamics
  • Transcription, Genetic

Substances

  • Proteins