| Autor: |
Savintseva LA; Department of Chemistry, Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia., Steshin IS; Department of Chemistry, Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia., Avdoshin AA; Department of Chemistry, Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia., Panteleev SV; Department of Chemistry, Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia., Rozhkov AV; Department of Chemistry, Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia., Shirokova EA; Department of Chemistry, Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia., Livshits GD; Department of Chemistry, Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia., Vasyankin AV; Department of Chemistry, Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia., Radchenko EV; Department of Chemistry, Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia.; Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia., Ignatov SK; Department of Chemistry, Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia., Palyulin VA; Department of Chemistry, Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia.; Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia. |
| Abstrakt: |
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. |
