Lipid II as a Target for Novel Antibiotics:Structural and Molecular Dynamics Studies.

Russian Journal of Bioorganic Chemistry. 2018. Vol. 44. No. 6. P. 653–664.

Panina I. S., Chugunov A., Efremov R.

The growing problem of antibiotic resistance in medicine raises the attention to antimicrobial substances that act on non-protein molecules, which have more conservative structure comparing to proteins or peptides. One of the most promising and studied targets is lipid II — the participant of the bacterial cell wall biosynthetic pathway. Lipid II is present in the bacterial membrane only and has a conservative chemical structure. There are several classes of natural antibiotics acting on lipid II, some of which block the peptidoglycan synthesis by formation of a strong complex with lipid II, and others have an additional bactericidal mechanism involved a violation of the membrane integrity. This review examines the prospects for using such antibacterial substances as new drugs to combat antibiotic-resistant pathogens. The main emphasis is made on the studies of membrane-embedded lipid II structure and molecular mechanisms of its recognition by water-soluble antibiotics, and also on computer modelling of their interaction.

Keywords: молекулярная динамика, биомембраны, antimicrobial peptides, intermolecular recognition, biomembranes, computer simulation of macromolecules, molecular dynamics, антимикробные пептиды, межмолекулярное распознавание, компьютерное моделирование макромолекул

Publication based on the results of: ­­­Atomistic multiscale modeling of properties and processes in materials and living systems; analysis of efficiency of new supercomputer technologies (2018)