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Entropy (Basel). 2015 May;17(5):2895-2918. Epub 2015 May 7.

AIM for Allostery: Using the Ising Model to Understand Information Processing and Transmission in Allosteric Biomolecular Systems.

Author information

  • 1Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
  • 2Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA ; HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute of Computational Biomedicine, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.

Abstract

In performing their biological functions, molecular machines must process and transmit information with high fidelity. Information transmission requires dynamic coupling between the conformations of discrete structural components within the protein positioned far from one another on the molecular scale. This type of biomolecular "action at a distance" is termed allostery. Although allostery is ubiquitous in biological regulation and signal transduction, its treatment in theoretical models has mostly eschewed quantitative descriptions involving the system's underlying structural components and their interactions. Here, we show how Ising models can be used to formulate an approach to allostery in a structural context of interactions between the constitutive components by building simple allosteric constructs we termed Allosteric Ising Models (AIMs). We introduce the use of AIMs in analytical and numerical calculations that relate thermodynamic descriptions of allostery to the structural context, and then show that many fundamental properties of allostery, such as the multiplicative property of parallel allosteric channels, are revealed from the analysis of such models. The power of exploring mechanistic structural models of allosteric function in more complex systems by using AIMs is demonstrated by building a model of allosteric signaling for an experimentally well-characterized asymmetric homodimer of the dopamine D2 receptor.

KEYWORDS:

G protein coupled receptors (GPCRs); Ising model; allostery; biophysics; dopamine D2 receptor; functional selectivity; information theory; signal transduction; statistical mechanics

PMID:
26594108
PMCID:
PMC4652859
DOI:
10.3390/e17052895
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