Abstract
Pseudomonas aeruginosa is a unique microorganism among the antibiotic-resistant microbial pathogens. Among the various therapeutic approaches, antimicrobial peptides are effective to combat this infection. The chimera C3 is a peptide derived from the human beta-defensins 2 and 3 that has previously displayed antibacterial activity against the Gram-negative and Gram-positive bacteria. In this research, the antibacterial activity and the effect of a new genetically designed chimera C3 (i.e. chimera C3-3) on the bacterial membrane was assessed by molecular dynamics (MD) simulation. To investigate the interactions of the peptide with the lipid bilayer model and their effects on each other, the characterizations e.g. Area Per Lipid (APL), density, deuterium order parameter, membrane thickness, Mean Square Displacement (MSD), Radial Distribution Function (RDF), hydrogen bonds (H-bond), root-mean-square-fluctuation (RMSF), bending modulus (KC) and free energy (ΔG) were compared between C3 and C3-3 peptides. Furthermore, the MD simulation of the pure membrane was also carried out. Finally, the comparison of the antibacterial effects showed that chimera C3-3 had the less antibacterial effect than the chimera C3 due to the N-terminal deletion of GII residues. Moreover, the results confirmed that the GII residue played the main role of an anchor in binding the membrane and deletion of anchor reduced the antibacterial activity.
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Acknowledgements
The authors are grateful to Shahed University for support of this work. We also thank Mr. Reza Talandashti and Dr. Ammar Mohseni for their cooperation. The authors are also grateful to Sana Alavi for re-reading and language/editing assistance. We also appreciate the manufacturers and developers of Gromacs, Chimera, VMD, Fatslime and Gridmat Software. Some molecular graphics and analyses were performed by the UCSF Chimera package. Chimera is developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIGMS P41-GM103311). Finally, we would like to thank all the people who have direct or indirect involvement in this work and their names have probably been forgotten.
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Ghafari, M.D., Rasooli, I., Khajeh, K. et al. Molecular Dynamics Study of the Human Beta-defensins 2 and 3 Chimeric Peptides with the Cell Membrane Model of Pseudomonas aeruginosa. Int J Pept Res Ther 26, 2039–2056 (2020). https://doi.org/10.1007/s10989-019-10000-x
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DOI: https://doi.org/10.1007/s10989-019-10000-x