Molecular dynamics simulation of the M2 helices within the nicotinic acetylcholine receptor transmembrane domain: structure and collective motions.
Multiple nanosecond duration molecular dynamics simulations were performed on the transmembrane region of the Torpedo nicotinic acetylcholine receptor embedded within a bilayer mimetic octane slab. The M2 helices and M2-M3 loop regions were free to move, whereas the outer (M1, M3, M4) helix bundle w...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2005
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| _version_ | 1826303815206305792 |
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| author | Hung, A Tai, K Sansom, M |
| author_facet | Hung, A Tai, K Sansom, M |
| author_sort | Hung, A |
| collection | OXFORD |
| description | Multiple nanosecond duration molecular dynamics simulations were performed on the transmembrane region of the Torpedo nicotinic acetylcholine receptor embedded within a bilayer mimetic octane slab. The M2 helices and M2-M3 loop regions were free to move, whereas the outer (M1, M3, M4) helix bundle was backbone restrained. The M2 helices largely retain their hydrogen-bonding pattern throughout the simulation, with some distortions in the helical end and loop regions. All of the M2 helices exhibit bending motions, with the hinge point in the vicinity of the central hydrophobic gate region (corresponding to residues alphaL251 and alphaV255). The bending motions of the M2 helices lead to a degree of dynamic narrowing of the pore in the region of the proposed hydrophobic gate. Calculations of Born energy profiles for various structures along the simulation trajectory suggest that the conformations of the M2 bundle sampled correspond to a closed conformation of the channel. Principal components analyses of each of the M2 helices, and of the five-helix M2 bundle, reveal concerted motions that may be relevant to channel function. Normal mode analyses using the anisotropic network model reveal collective motions similar to those identified by principal components analyses. |
| first_indexed | 2024-03-07T06:08:25Z |
| format | Journal article |
| id | oxford-uuid:eea27c97-204e-4835-896e-f63693de1de6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:08:25Z |
| publishDate | 2005 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:eea27c97-204e-4835-896e-f63693de1de62022-03-27T11:34:17ZMolecular dynamics simulation of the M2 helices within the nicotinic acetylcholine receptor transmembrane domain: structure and collective motions.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:eea27c97-204e-4835-896e-f63693de1de6EnglishSymplectic Elements at OxfordElsevier2005Hung, ATai, KSansom, MMultiple nanosecond duration molecular dynamics simulations were performed on the transmembrane region of the Torpedo nicotinic acetylcholine receptor embedded within a bilayer mimetic octane slab. The M2 helices and M2-M3 loop regions were free to move, whereas the outer (M1, M3, M4) helix bundle was backbone restrained. The M2 helices largely retain their hydrogen-bonding pattern throughout the simulation, with some distortions in the helical end and loop regions. All of the M2 helices exhibit bending motions, with the hinge point in the vicinity of the central hydrophobic gate region (corresponding to residues alphaL251 and alphaV255). The bending motions of the M2 helices lead to a degree of dynamic narrowing of the pore in the region of the proposed hydrophobic gate. Calculations of Born energy profiles for various structures along the simulation trajectory suggest that the conformations of the M2 bundle sampled correspond to a closed conformation of the channel. Principal components analyses of each of the M2 helices, and of the five-helix M2 bundle, reveal concerted motions that may be relevant to channel function. Normal mode analyses using the anisotropic network model reveal collective motions similar to those identified by principal components analyses. |
| spellingShingle | Hung, A Tai, K Sansom, M Molecular dynamics simulation of the M2 helices within the nicotinic acetylcholine receptor transmembrane domain: structure and collective motions. |
| title | Molecular dynamics simulation of the M2 helices within the nicotinic acetylcholine receptor transmembrane domain: structure and collective motions. |
| title_full | Molecular dynamics simulation of the M2 helices within the nicotinic acetylcholine receptor transmembrane domain: structure and collective motions. |
| title_fullStr | Molecular dynamics simulation of the M2 helices within the nicotinic acetylcholine receptor transmembrane domain: structure and collective motions. |
| title_full_unstemmed | Molecular dynamics simulation of the M2 helices within the nicotinic acetylcholine receptor transmembrane domain: structure and collective motions. |
| title_short | Molecular dynamics simulation of the M2 helices within the nicotinic acetylcholine receptor transmembrane domain: structure and collective motions. |
| title_sort | molecular dynamics simulation of the m2 helices within the nicotinic acetylcholine receptor transmembrane domain structure and collective motions |
| work_keys_str_mv | AT hunga moleculardynamicssimulationofthem2heliceswithinthenicotinicacetylcholinereceptortransmembranedomainstructureandcollectivemotions AT taik moleculardynamicssimulationofthem2heliceswithinthenicotinicacetylcholinereceptortransmembranedomainstructureandcollectivemotions AT sansomm moleculardynamicssimulationofthem2heliceswithinthenicotinicacetylcholinereceptortransmembranedomainstructureandcollectivemotions |