Role of Peptide Associations in Enhancing the Antimicrobial Activity of Adepantins: Comparative Molecular Dynamics Simulations and Design Assessments.

Autor: Maleš M; Faculty of Maritime Studies, University of Split, 21000 Split, Croatia., Juretić D; Department of Physics, Faculty of Science, University of Split, 21000 Split, Croatia., Zoranić L; Department of Physics, Faculty of Science, University of Split, 21000 Split, Croatia.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Nov 08; Vol. 25 (22). Date of Electronic Publication: 2024 Nov 08.
DOI: 10.3390/ijms252212009
Abstrakt: Adepantins are peptides designed to optimize antimicrobial biological activity through the choice of specific amino acid residues, resulting in helical and amphipathic structures. This paper focuses on revealing the atomistic details of the mechanism of action of Adepantins and aligning design concepts with peptide behavior through simulation results. Notably, Adepantin-1a exhibits a broad spectrum of activity against both Gram-positive and Gram-negative bacteria, while Adepantin-1 has a narrow spectrum of activity against Gram-negative bacteria. The simulation results showed that one of the main differences is the extent of aggregation. Both peptides exhibit a strong tendency to cluster due to the amphipathicity embedded during design process. However, the more potent Adepantin-1a forms smaller aggregates than Adepantin-1, confirming the idea that the optimal aggregations, not the strongest aggregations, favor activity. Additionally, we show that incorporation of the cell penetration region affects the mechanisms of action of Adepantin-1a and promotes stronger binding to anionic and neutral membranes.
Databáze: MEDLINE
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