Mechanical Coupling in Myosin V: A Simulation Study
Myosin motor function depends on the interaction between different domains that transmit information from one part of the molecule to another. The interdomain coupling in myosin V is studied with restrained targeted molecular dynamics using an all-atom representation in explicit solvent. To elucidat...
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| Format: | Article |
| Language: | en_US |
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Elsevier B.V.
2013
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| Online Access: | http://hdl.handle.net/1721.1/79380 https://orcid.org/0000-0003-1417-9470 |
| _version_ | 1811085800450818048 |
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| author | Ovchinnikov, Victor Trout, Bernhardt L. Karplus, Martin |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Ovchinnikov, Victor Trout, Bernhardt L. Karplus, Martin |
| author_sort | Ovchinnikov, Victor |
| collection | MIT |
| description | Myosin motor function depends on the interaction between different domains that transmit information from one part of the molecule to another. The interdomain coupling in myosin V is studied with restrained targeted molecular dynamics using an all-atom representation in explicit solvent. To elucidate the origin of the conformational change due to the binding of ATP, targeting forces are applied to small sets of atoms (the forcing sets, FSs) in the direction of their displacement from the rigor conformation, which has a closed actin-binding cleft, to the post-rigor conformation, in which the cleft is open. The “minimal” FS that results in extensive structural changes in the overall myosin conformation is composed of ATP, switch 1, and the nearby HF, HG, and HH helices. Addition of switch 2 to the FS is required to achieve a complete opening of the actin-binding cleft. The restrained targeted molecular dynamics simulations reveal the mechanical coupling pathways between (i) the nucleotide-binding pocket (NBP) and the actin-binding cleft, (ii) the NBP and the converter, and (iii) the actin-binding cleft and the converter. Closing of the NBP due to ATP binding is tightly coupled to the opening of the cleft and leads to the rupture of a key hydrogen bond (F441N/A684O) between switch 2 and the SH1 helix. The actin-binding cleft may mediate the rupture of this bond via a connection between the HW helix, the relay helix, and switch 2. The findings are consistent with experimental studies and a recent normal mode analysis. The present method is expected to be useful more generally in studies of interdomain coupling in proteins. |
| first_indexed | 2024-09-23T13:15:52Z |
| format | Article |
| id | mit-1721.1/79380 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:15:52Z |
| publishDate | 2013 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/793802022-09-28T12:59:51Z Mechanical Coupling in Myosin V: A Simulation Study Ovchinnikov, Victor Trout, Bernhardt L. Karplus, Martin Massachusetts Institute of Technology. Department of Chemical Engineering Ovchinnikov, Victor Trout, Bernhardt L. Myosin motor function depends on the interaction between different domains that transmit information from one part of the molecule to another. The interdomain coupling in myosin V is studied with restrained targeted molecular dynamics using an all-atom representation in explicit solvent. To elucidate the origin of the conformational change due to the binding of ATP, targeting forces are applied to small sets of atoms (the forcing sets, FSs) in the direction of their displacement from the rigor conformation, which has a closed actin-binding cleft, to the post-rigor conformation, in which the cleft is open. The “minimal” FS that results in extensive structural changes in the overall myosin conformation is composed of ATP, switch 1, and the nearby HF, HG, and HH helices. Addition of switch 2 to the FS is required to achieve a complete opening of the actin-binding cleft. The restrained targeted molecular dynamics simulations reveal the mechanical coupling pathways between (i) the nucleotide-binding pocket (NBP) and the actin-binding cleft, (ii) the NBP and the converter, and (iii) the actin-binding cleft and the converter. Closing of the NBP due to ATP binding is tightly coupled to the opening of the cleft and leads to the rupture of a key hydrogen bond (F441N/A684O) between switch 2 and the SH1 helix. The actin-binding cleft may mediate the rupture of this bond via a connection between the HW helix, the relay helix, and switch 2. The findings are consistent with experimental studies and a recent normal mode analysis. The present method is expected to be useful more generally in studies of interdomain coupling in proteins. 2013-06-27T19:36:55Z 2013-06-27T19:36:55Z 2009-10 2009-10 Article http://purl.org/eprint/type/JournalArticle 00222836 1089-8638 http://hdl.handle.net/1721.1/79380 Ovchinnikov, Victor, Bernhardt L. Trout, and Martin Karplus. Mechanical Coupling in Myosin V: A Simulation Study. Journal of Molecular Biology 395, no. 4 (January 2010): 815-833. https://orcid.org/0000-0003-1417-9470 en_US http://dx.doi.org/10.1016/j.jmb.2009.10.029 Journal of Molecular Biology Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Elsevier B.V. PMC |
| spellingShingle | Ovchinnikov, Victor Trout, Bernhardt L. Karplus, Martin Mechanical Coupling in Myosin V: A Simulation Study |
| title | Mechanical Coupling in Myosin V: A Simulation Study |
| title_full | Mechanical Coupling in Myosin V: A Simulation Study |
| title_fullStr | Mechanical Coupling in Myosin V: A Simulation Study |
| title_full_unstemmed | Mechanical Coupling in Myosin V: A Simulation Study |
| title_short | Mechanical Coupling in Myosin V: A Simulation Study |
| title_sort | mechanical coupling in myosin v a simulation study |
| url | http://hdl.handle.net/1721.1/79380 https://orcid.org/0000-0003-1417-9470 |
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