Temperature-Induced Restructuring of Mycolic Acid Bilayers Modeling the <i>Mycobacterium tuberculosis</i> Outer Membrane: A Molecular Dynamics Study
The emergence of new drug-resistant strains of the tuberculosis pathogen <i>Mycobacterium tuberculosis</i> (Mtb) is a new challenge for modern medicine. Its resistance capacity is closely related to the properties of the outer membrane of the Mtb cell wall, which is a bilayer membrane fo...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-02-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/29/3/696 |
| _version_ | 1797318417915576320 |
|---|---|
| author | Alexander V. Vasyankin Sergey V. Panteleev Ilya S. Steshin Ekaterina A. Shirokova Alexey V. Rozhkov Grigory D. Livshits Eugene V. Radchenko Stanislav K. Ignatov Vladimir A. Palyulin |
| author_facet | Alexander V. Vasyankin Sergey V. Panteleev Ilya S. Steshin Ekaterina A. Shirokova Alexey V. Rozhkov Grigory D. Livshits Eugene V. Radchenko Stanislav K. Ignatov Vladimir A. Palyulin |
| author_sort | Alexander V. Vasyankin |
| collection | DOAJ |
| description | The emergence of new drug-resistant strains of the tuberculosis pathogen <i>Mycobacterium tuberculosis</i> (Mtb) is a new challenge for modern medicine. Its resistance capacity is closely related to the properties of the outer membrane of the Mtb cell wall, which is a bilayer membrane formed by mycolic acids (MAs) and their derivatives. To date, the molecular mechanisms of the response of the Mtb outer membrane to external factors and, in particular, elevated temperatures have not been sufficiently studied. In this work, we consider the temperature-induced changes in the structure, ordering, and molecular mobility of bilayer MA membranes of various chemical and conformational compositions. Using all-atom long-term molecular dynamics simulations of various MA membranes, we report the kinetic parameters of temperature-dependent changes in the MA self-diffusion coefficients and conformational compositions, including the apparent activation energies of these processes, as well as the characteristic times of ordering changes and the features of phase transitions occurring over a wide range of elevated temperatures. Understanding these effects could be useful for the prevention of drug resistance and the development of membrane-targeting pharmaceuticals, as well as in the design of membrane-based materials. |
| first_indexed | 2024-03-08T03:51:54Z |
| format | Article |
| id | doaj.art-91022b6292434f50b760e355ed76b769 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-08T03:51:54Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-91022b6292434f50b760e355ed76b7692024-02-09T15:19:08ZengMDPI AGMolecules1420-30492024-02-0129369610.3390/molecules29030696Temperature-Induced Restructuring of Mycolic Acid Bilayers Modeling the <i>Mycobacterium tuberculosis</i> Outer Membrane: A Molecular Dynamics StudyAlexander V. Vasyankin0Sergey V. Panteleev1Ilya S. Steshin2Ekaterina A. Shirokova3Alexey V. Rozhkov4Grigory D. Livshits5Eugene V. Radchenko6Stanislav K. Ignatov7Vladimir A. Palyulin8Department of Chemistry, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod 603022, RussiaDepartment of Chemistry, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod 603022, RussiaDepartment of Chemistry, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod 603022, RussiaDepartment of Chemistry, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod 603022, RussiaDepartment of Chemistry, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod 603022, RussiaDepartment of Chemistry, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod 603022, RussiaDepartment of Chemistry, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod 603022, RussiaDepartment of Chemistry, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod 603022, RussiaDepartment of Chemistry, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod 603022, RussiaThe emergence of new drug-resistant strains of the tuberculosis pathogen <i>Mycobacterium tuberculosis</i> (Mtb) is a new challenge for modern medicine. Its resistance capacity is closely related to the properties of the outer membrane of the Mtb cell wall, which is a bilayer membrane formed by mycolic acids (MAs) and their derivatives. To date, the molecular mechanisms of the response of the Mtb outer membrane to external factors and, in particular, elevated temperatures have not been sufficiently studied. In this work, we consider the temperature-induced changes in the structure, ordering, and molecular mobility of bilayer MA membranes of various chemical and conformational compositions. Using all-atom long-term molecular dynamics simulations of various MA membranes, we report the kinetic parameters of temperature-dependent changes in the MA self-diffusion coefficients and conformational compositions, including the apparent activation energies of these processes, as well as the characteristic times of ordering changes and the features of phase transitions occurring over a wide range of elevated temperatures. Understanding these effects could be useful for the prevention of drug resistance and the development of membrane-targeting pharmaceuticals, as well as in the design of membrane-based materials.https://www.mdpi.com/1420-3049/29/3/696tuberculosismycobacteriumcell wallouter membranetemperature induced conformational changesdiffusion constants |
| spellingShingle | Alexander V. Vasyankin Sergey V. Panteleev Ilya S. Steshin Ekaterina A. Shirokova Alexey V. Rozhkov Grigory D. Livshits Eugene V. Radchenko Stanislav K. Ignatov Vladimir A. Palyulin Temperature-Induced Restructuring of Mycolic Acid Bilayers Modeling the <i>Mycobacterium tuberculosis</i> Outer Membrane: A Molecular Dynamics Study Molecules tuberculosis mycobacterium cell wall outer membrane temperature induced conformational changes diffusion constants |
| title | Temperature-Induced Restructuring of Mycolic Acid Bilayers Modeling the <i>Mycobacterium tuberculosis</i> Outer Membrane: A Molecular Dynamics Study |
| title_full | Temperature-Induced Restructuring of Mycolic Acid Bilayers Modeling the <i>Mycobacterium tuberculosis</i> Outer Membrane: A Molecular Dynamics Study |
| title_fullStr | Temperature-Induced Restructuring of Mycolic Acid Bilayers Modeling the <i>Mycobacterium tuberculosis</i> Outer Membrane: A Molecular Dynamics Study |
| title_full_unstemmed | Temperature-Induced Restructuring of Mycolic Acid Bilayers Modeling the <i>Mycobacterium tuberculosis</i> Outer Membrane: A Molecular Dynamics Study |
| title_short | Temperature-Induced Restructuring of Mycolic Acid Bilayers Modeling the <i>Mycobacterium tuberculosis</i> Outer Membrane: A Molecular Dynamics Study |
| title_sort | temperature induced restructuring of mycolic acid bilayers modeling the i mycobacterium tuberculosis i outer membrane a molecular dynamics study |
| topic | tuberculosis mycobacterium cell wall outer membrane temperature induced conformational changes diffusion constants |
| url | https://www.mdpi.com/1420-3049/29/3/696 |
| work_keys_str_mv | AT alexandervvasyankin temperatureinducedrestructuringofmycolicacidbilayersmodelingtheimycobacteriumtuberculosisioutermembraneamoleculardynamicsstudy AT sergeyvpanteleev temperatureinducedrestructuringofmycolicacidbilayersmodelingtheimycobacteriumtuberculosisioutermembraneamoleculardynamicsstudy AT ilyassteshin temperatureinducedrestructuringofmycolicacidbilayersmodelingtheimycobacteriumtuberculosisioutermembraneamoleculardynamicsstudy AT ekaterinaashirokova temperatureinducedrestructuringofmycolicacidbilayersmodelingtheimycobacteriumtuberculosisioutermembraneamoleculardynamicsstudy AT alexeyvrozhkov temperatureinducedrestructuringofmycolicacidbilayersmodelingtheimycobacteriumtuberculosisioutermembraneamoleculardynamicsstudy AT grigorydlivshits temperatureinducedrestructuringofmycolicacidbilayersmodelingtheimycobacteriumtuberculosisioutermembraneamoleculardynamicsstudy AT eugenevradchenko temperatureinducedrestructuringofmycolicacidbilayersmodelingtheimycobacteriumtuberculosisioutermembraneamoleculardynamicsstudy AT stanislavkignatov temperatureinducedrestructuringofmycolicacidbilayersmodelingtheimycobacteriumtuberculosisioutermembraneamoleculardynamicsstudy AT vladimirapalyulin temperatureinducedrestructuringofmycolicacidbilayersmodelingtheimycobacteriumtuberculosisioutermembraneamoleculardynamicsstudy |