| Autor: |
Pokhrel R, Bhattarai N, Baral P, Gerstman BS, Park JH; Oragenics Inc., Alachua, Florida 32615, United States., Handfield M; Oragenics Inc., Alachua, Florida 32615, United States., Chapagain PP |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of chemical theory and computation [J Chem Theory Comput] 2022 Jan 11; Vol. 18 (1), pp. 516-525. Date of Electronic Publication: 2021 Dec 07. |
| DOI: |
10.1021/acs.jctc.1c00666 |
| Abstrakt: |
There has been an alarming rise in antibacterial resistant infections in recent years due to the widespread use of antibiotics, and there is a dire need for the development of new antibiotics utilizing novel modes of action. Lantibiotics are promising candidates to engage in the fight against resistant strains of bacteria due to their unique modes of action, including interference with cell wall synthesis by binding to lipid II and creating pores in bacterial membranes. In this study, we use atomic-scale molecular dynamics computational studies to compare both the lipid II binding ability and the membrane interactions of five lanthipeptides that are commonly used in antimicrobial research: nisin, Mutacin 1140 (MU1140), gallidermin, NVB302, and NAI107. Among the five peptides investigated, nisin is found to be the most efficient at forming water channels through a membrane, whereas gallidermin and MU1140 are found to be better at binding the lipid II molecules. Nisin's effectiveness in facilitating water transport across the membrane is due to the creation of several different water trajectories along with no significant water delay points along the paths. The shorter peptide deoxyactagardine B (NVB302) was found to not form a water channel. These detailed observations provide insights into the dual mechanisms of the action of lantibiotic peptides and can facilitate the design and development of novel lanthipeptides by strategic placement of different residues. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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