The emergence of new drug-resistant strains of the tuberculosis pathogen Mycobacterium tuberculosis (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.
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Nagoya Univ, Ctr Computat Sci, Grad Sch Engn, Chikusa Ku, Furo Cho, Nagoya, Aichi 4648603, JapanNagoya Univ, Ctr Computat Sci, Grad Sch Engn, Chikusa Ku, Furo Cho, Nagoya, Aichi 4648603, Japan
Andoh, Yoshimichi
Hayakawa, Shiho
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Nagoya Univ, Dept Mat Chem, Chikusa Ku, Furo Cho, Nagoya, Aichi 4648603, JapanNagoya Univ, Ctr Computat Sci, Grad Sch Engn, Chikusa Ku, Furo Cho, Nagoya, Aichi 4648603, Japan
Hayakawa, Shiho
Okazaki, Susumu
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Nagoya Univ, Dept Mat Chem, Chikusa Ku, Furo Cho, Nagoya, Aichi 4648603, Japan
Univ Tokyo, Dept Adv Mat Sci, Kashiwa, Chiba 2278561, JapanNagoya Univ, Ctr Computat Sci, Grad Sch Engn, Chikusa Ku, Furo Cho, Nagoya, Aichi 4648603, Japan