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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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