Binding mechanism of two PaDBS1 derived peptides with different phospholipid membranes and its coarse-grained molecular dynamics analysis
Shandong Province Key Laboratory of Medical Physics and Image Processing Technology, School of Physics and Electronics, Shandong Normal University, 250358, Jinan, People’s Republic of China
Accepted: 19 July 2022
Published online: 4 August 2022
Facing the serious crisis of antibiotic resistance, the utilization of antimicrobial peptides (AMPs) is becoming extraordinarily imperative, and accompanied with it, understanding the action mechanism of newly synthesized AMPs is also extremely urgent. In this paper, we used the coarse-grained (CG) molecular dynamics method to study the physical mechanism of natural AMP PaDBS1 and its two derivative peptides PaDBS1R1 (2n9r) and PaDBS1R6 (6cfa) acting on different phospholipid membranes. The Gram-negative bacterial membrane was formed by CG models POPC and POPG, and the mammalian cell membrane was composed by individual POPC, from which six simulation systems were also constructed. The simulation shows that compared with the inactive natural AMP PaDBS1, 2n9r and 6cfa display the definite activities against Gram-negative bacteria with much higher activity of 6cfa than 2n9r. Their action mechanism relies mainly on a combination of electrostatic interaction and hydrophobic interaction, which is also closely related to the binding mode of the phospholipid membrane. The peptide-membrane interaction gives rise to the changes of the phospholipid membrane structure, such as its thickness, surface area and fluidity, and so on. The present work can not only help to comprehend the interaction process between AMPs and cell membrane, but also be beneficial to the research and development of new antimicrobials.
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