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Conformational Dynamics and Stability of Bilayers Formed by Mycolic Acids from the Mycobacterium tuberculosis Outer Membrane
Bilayers of mycolic acids (MAs) form the outer membrane of Mycobacterium tuberculosis that has high strength and extremely low permeability for external molecules (including antibiotics). For the first time, we were able to study them using the all-atom long-term molecular dynamic simulations (from...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9921641/ https://www.ncbi.nlm.nih.gov/pubmed/36771014 http://dx.doi.org/10.3390/molecules28031347 |
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author | Savintseva, Liana A. Steshin, Ilya S. Avdoshin, Alexander A. Panteleev, Sergey V. Rozhkov, Alexey V. Shirokova, Ekaterina A. Livshits, Grigory D. Vasyankin, Alexander V. Radchenko, Eugene V. Ignatov, Stanislav K. Palyulin, Vladimir A. |
author_facet | Savintseva, Liana A. Steshin, Ilya S. Avdoshin, Alexander A. Panteleev, Sergey V. Rozhkov, Alexey V. Shirokova, Ekaterina A. Livshits, Grigory D. Vasyankin, Alexander V. Radchenko, Eugene V. Ignatov, Stanislav K. Palyulin, Vladimir A. |
author_sort | Savintseva, Liana A. |
collection | PubMed |
description | Bilayers of mycolic acids (MAs) form the outer membrane of Mycobacterium tuberculosis that has high strength and extremely low permeability for external molecules (including antibiotics). For the first time, we were able to study them using the all-atom long-term molecular dynamic simulations (from 300 ns up to 1.2 μs) in order to investigate the conformational changes and most favorable structures of the mycobacterial membranes. The structure and properties of the membranes are crucially dependent on the initial packing of the α-mycolic acid (AMA) molecules, as well as on the presence of the secondary membrane components, keto- and methoxy mycolic acids (KMAs and MMAs). In the case of AMA-based membranes, the most labile conformation is W while other types of conformations (sU as well as sZ, eU, and eZ) are much more stable. In the multicomponent membranes, the presence of the KMA and MMA components (in the W conformation) additionally stabilizes both the W and eU conformations of AMA. The membrane in which AMA prevails in the eU conformation is much thicker and, at the same time, much denser. Such a packing of the MA molecules promotes the formation of a significantly stronger outer mycobacterial membrane that should be much more resistant to the threatening external factors. |
format | Online Article Text |
id | pubmed-9921641 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99216412023-02-12 Conformational Dynamics and Stability of Bilayers Formed by Mycolic Acids from the Mycobacterium tuberculosis Outer Membrane Savintseva, Liana A. Steshin, Ilya S. Avdoshin, Alexander A. Panteleev, Sergey V. Rozhkov, Alexey V. Shirokova, Ekaterina A. Livshits, Grigory D. Vasyankin, Alexander V. Radchenko, Eugene V. Ignatov, Stanislav K. Palyulin, Vladimir A. Molecules Article Bilayers of mycolic acids (MAs) form the outer membrane of Mycobacterium tuberculosis that has high strength and extremely low permeability for external molecules (including antibiotics). For the first time, we were able to study them using the all-atom long-term molecular dynamic simulations (from 300 ns up to 1.2 μs) in order to investigate the conformational changes and most favorable structures of the mycobacterial membranes. The structure and properties of the membranes are crucially dependent on the initial packing of the α-mycolic acid (AMA) molecules, as well as on the presence of the secondary membrane components, keto- and methoxy mycolic acids (KMAs and MMAs). In the case of AMA-based membranes, the most labile conformation is W while other types of conformations (sU as well as sZ, eU, and eZ) are much more stable. In the multicomponent membranes, the presence of the KMA and MMA components (in the W conformation) additionally stabilizes both the W and eU conformations of AMA. The membrane in which AMA prevails in the eU conformation is much thicker and, at the same time, much denser. Such a packing of the MA molecules promotes the formation of a significantly stronger outer mycobacterial membrane that should be much more resistant to the threatening external factors. MDPI 2023-01-31 /pmc/articles/PMC9921641/ /pubmed/36771014 http://dx.doi.org/10.3390/molecules28031347 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Savintseva, Liana A. Steshin, Ilya S. Avdoshin, Alexander A. Panteleev, Sergey V. Rozhkov, Alexey V. Shirokova, Ekaterina A. Livshits, Grigory D. Vasyankin, Alexander V. Radchenko, Eugene V. Ignatov, Stanislav K. Palyulin, Vladimir A. Conformational Dynamics and Stability of Bilayers Formed by Mycolic Acids from the Mycobacterium tuberculosis Outer Membrane |
title | Conformational Dynamics and Stability of Bilayers Formed by Mycolic Acids from the Mycobacterium tuberculosis Outer Membrane |
title_full | Conformational Dynamics and Stability of Bilayers Formed by Mycolic Acids from the Mycobacterium tuberculosis Outer Membrane |
title_fullStr | Conformational Dynamics and Stability of Bilayers Formed by Mycolic Acids from the Mycobacterium tuberculosis Outer Membrane |
title_full_unstemmed | Conformational Dynamics and Stability of Bilayers Formed by Mycolic Acids from the Mycobacterium tuberculosis Outer Membrane |
title_short | Conformational Dynamics and Stability of Bilayers Formed by Mycolic Acids from the Mycobacterium tuberculosis Outer Membrane |
title_sort | conformational dynamics and stability of bilayers formed by mycolic acids from the mycobacterium tuberculosis outer membrane |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9921641/ https://www.ncbi.nlm.nih.gov/pubmed/36771014 http://dx.doi.org/10.3390/molecules28031347 |
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