Journal Article

A general mechanism for signal propagation in the nicotinic acetylcholine receptor family


Nicotinic acetylcholine receptors (nAChRs) modulate synaptic activity in the central nervous system. The α7 subtype, in particular, has attracted considerable interest in drug discovery as a target for several conditions, including Alzheimer’s disease and schizophrenia. Identifying agonist-induced structural changes underlying nAChR activation is fundamentally important for understanding biological function and rational drug design. Here, extensive equilibrium and nonequilibrium molecular dynamics simulations, enabled by cloud-based high-performance computing, reveal the molecular mechanism by which structural changes induced by agonist unbinding are transmitted within the human α7 nAChR. The simulations reveal the sequence of coupled structural changes involved in driving conformational change responsible for biological function. Comparison with simulations of the α4β2 nAChR subtype identifies features of the dynamical architecture common to both receptors, suggesting a general structural mechanism for signal propagation in this important family of receptors.

Attached files


Oliveira, Ana Sofia F.
Edsall, Christopher J.
Woods, Christopher J.
Bates, Phil
Nunez, Gerardo V.
Wonnacott, Susan
Bermudez, Isabel
Ciccotti, Giovanni
Gallagher, Timothy
Sessions, Richard B.
Mulholland, Adrian J.

Oxford Brookes departments

Department of Biological and Medical Sciences


Year of publication: 2019
Date of RADAR deposit: 2019-12-09

Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License

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