Temperature-Induced Restructuring of Mycolic Acid Bilayers Modeling the Outer Membrane: A Molecular Dynamics Study.

The emergence of new drug-resistant strains of the tuberculosis pathogen (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.

Free Energy Barriers for Passive Drug Transport through the Outer Membrane: A Molecular Dynamics Study.

The emergence of multi-drug-resistant tuberculosis strains poses a significant challenge to modern medicine. The development of new antituberculosis drugs is hindered by the low permeability of many active compounds through the extremely strong bacterial cell wall of mycobacteria. In order to estimate the ability of potential antimycobacterial agents to diffuse through the outer mycolate membrane, the free energy profiles, the corresponding activation barriers, and possible permeability modes of passive transport for a series of known antibiotics, modern antituberculosis drugs, and prospective active drug-like molecules were determined using molecular dynamics simulations with the all-atom force field and potential of mean-force calculations.

Conformational Dynamics and Stability of Bilayers Formed by Mycolic Acids from the Outer Membrane.

Bilayers of mycolic acids (MAs) form the outer membrane of 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.

Effect of Polyvinylidene Fluoride Membrane Production Conditions on Its Structure and Performance Characteristics.

Poly (vinylidene fluoride) membranes were prepared by freeze-casting. The effects of PVDF concentration, and freezing temperature on the morphology, crystallization, and performance of prepared membranes were examined. Polymer concentration was varied from 10 to 25 wt%.