Projects per year
Abstract
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.
Original language | English |
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Article number | 51 |
Pages (from-to) | 19953-19958 |
Number of pages | 6 |
Journal | Journal of the American Chemical Society |
Volume | 141 |
Issue number | 51 |
Early online date | 6 Dec 2019 |
DOIs | |
Publication status | Published - 26 Dec 2019 |
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Dive into the research topics of 'A General Mechanism for Signal Propagation in the Nicotinic Acetylcholine Receptor Family'. Together they form a unique fingerprint.Projects
- 1 Finished
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CCP-BioSim: Biomolecular Simulation at the Life Sciences Interface
Mulholland, A. J. (Principal Investigator)
1/07/15 → 30/04/21
Project: Research
Equipment
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HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities
Alam, S. R. (Manager), Williams, D. A. G. (Manager), Eccleston, P. E. (Manager) & Greene, D. (Manager)
Facility/equipment: Facility
Profiles
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Professor Adrian J Mulholland
- Infection and Immunity
- School of Chemistry - Professor
Person: Academic , Member