Simulation studies of alamethicin-bilayer interactions
Alamethicin is an α-helical peptide that forms voltage-activated ion channels. Experimental data suggest that channel formation occurs via voltage-dependent insertion of alamethicin helices into lipid bilayers, followed by self-assembly of inserted helices to form a parallel helix bundle. Changes in...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Journal article |
| Language: | English |
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Elsevier
1997
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| Subjects: |
| _version_ | 1797094062280409088 |
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| author | Biggin, P Breed, J Son, H Sansom, M |
| author2 | Biophysical Society |
| author_facet | Biophysical Society Biggin, P Breed, J Son, H Sansom, M |
| author_sort | Biggin, P |
| collection | OXFORD |
| description | Alamethicin is an α-helical peptide that forms voltage-activated ion channels. Experimental data suggest that channel formation occurs via voltage-dependent insertion of alamethicin helices into lipid bilayers, followed by self-assembly of inserted helices to form a parallel helix bundle. Changes in the kink angle of the alamethicin helix about its central proline residue have also been suggested to play a role in channel gating. Alamethicin helices generated by simulated annealing and restrained molecular dynamics adopt a kink angle similar to that in the x-ray crystal structure, even if such simulations start with an idealized unkinked helix. This suggests that the kinked helix represents a stable conformation of the molecule. Molecular dynamics simulations in the presence of a simple bilayer model and a transbilayer voltage difference are used to explore possible mechanisms of helix insertion. The bilayer is represented by a hydrophobicity potential. An alamethicin helix inserts spontaneously in the absence of a transbilayer voltage. Application of a <em>cis</em> positive voltage decreases the time to insertion. The helix kink angle fluctuates during the simulations. Insertion of the helix is associated with a decrease in the mean kink angle, thus helping the alamethicin molecule to span the bilayer. The simulation results are discussed in terms of models of alamethicin channel gating. |
| first_indexed | 2024-03-07T04:08:55Z |
| format | Journal article |
| id | oxford-uuid:c72962fd-cfbb-45c5-8f04-dbf3cae7e423 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:08:55Z |
| publishDate | 1997 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:c72962fd-cfbb-45c5-8f04-dbf3cae7e4232022-03-27T06:43:04ZSimulation studies of alamethicin-bilayer interactionsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c72962fd-cfbb-45c5-8f04-dbf3cae7e423BiochemistryEnglishOxford University Research Archive - ValetElsevier1997Biggin, PBreed, JSon, HSansom, MBiophysical SocietyAlamethicin is an α-helical peptide that forms voltage-activated ion channels. Experimental data suggest that channel formation occurs via voltage-dependent insertion of alamethicin helices into lipid bilayers, followed by self-assembly of inserted helices to form a parallel helix bundle. Changes in the kink angle of the alamethicin helix about its central proline residue have also been suggested to play a role in channel gating. Alamethicin helices generated by simulated annealing and restrained molecular dynamics adopt a kink angle similar to that in the x-ray crystal structure, even if such simulations start with an idealized unkinked helix. This suggests that the kinked helix represents a stable conformation of the molecule. Molecular dynamics simulations in the presence of a simple bilayer model and a transbilayer voltage difference are used to explore possible mechanisms of helix insertion. The bilayer is represented by a hydrophobicity potential. An alamethicin helix inserts spontaneously in the absence of a transbilayer voltage. Application of a <em>cis</em> positive voltage decreases the time to insertion. The helix kink angle fluctuates during the simulations. Insertion of the helix is associated with a decrease in the mean kink angle, thus helping the alamethicin molecule to span the bilayer. The simulation results are discussed in terms of models of alamethicin channel gating. |
| spellingShingle | Biochemistry Biggin, P Breed, J Son, H Sansom, M Simulation studies of alamethicin-bilayer interactions |
| title | Simulation studies of alamethicin-bilayer interactions |
| title_full | Simulation studies of alamethicin-bilayer interactions |
| title_fullStr | Simulation studies of alamethicin-bilayer interactions |
| title_full_unstemmed | Simulation studies of alamethicin-bilayer interactions |
| title_short | Simulation studies of alamethicin-bilayer interactions |
| title_sort | simulation studies of alamethicin bilayer interactions |
| topic | Biochemistry |
| work_keys_str_mv | AT bigginp simulationstudiesofalamethicinbilayerinteractions AT breedj simulationstudiesofalamethicinbilayerinteractions AT sonh simulationstudiesofalamethicinbilayerinteractions AT sansomm simulationstudiesofalamethicinbilayerinteractions |