Jafari Majid, Mehrnejad Faramarz, Doustdar Farahnoosh
Department of Life Sciences Engineering, Faculty of New Sciences & Technologies, University of Tehran, Tehran, Iran.
Department of Microbiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
PLoS One. 2017 Nov 10;12(11):e0187216. doi: 10.1371/journal.pone.0187216. eCollection 2017.
Pardaxin, with a bend-helix-bend-helix structure, is a membrane-active antimicrobial peptide that its membrane activity depends on the lipid bilayer composition. Herein, all-atom molecular dynamics (MD) simulations were performed to provide further molecular insight into the interactions, structural dynamics, orientation behavior, and cationic residues snorkeling of pardaxin in the DMPC, DPPC, POPC, POPG, POPG/POPE (3:1), and POPG/POPE (1:3) lipid bilayers. The results showed that the C-terminal helix of the peptide was maintained in all six types of the model-bilayers and pardaxin was tilted into the DMPC, DPPC, and POPG/POPE mixed bilayers more than the POPC and POPG bilayers. As well as, the structure of zwitterionic membranes was more affected by the peptide than the anionic bilayers. Taken together, the study demonstrated that the cationic residues of pardaxin snorkeled toward the interface of lipid bilayers and all phenylalanine residues of the peptide played important roles in the peptide-membrane interactions. We hope that this work will provide a better understanding of the interactions of antimicrobial peptides with the membranes.
豹鳎毒素具有弯曲-螺旋-弯曲-螺旋结构，是一种膜活性抗菌肽，其膜活性取决于脂质双层的组成。在此，进行了全原子分子动力学（MD）模拟，以进一步从分子层面深入了解豹鳎毒素在二肉豆蔻酰磷脂酰胆碱（DMPC）、二棕榈酰磷脂酰胆碱（DPPC）、1-棕榈酰-2-油酰磷脂酰胆碱（POPC）、1-棕榈酰-2-油酰磷脂酰甘油（POPG）、POPG/1-棕榈酰-2-油酰磷脂酰乙醇胺（POPE）（3:1）和POPG/POPE（1:3）脂质双层中的相互作用、结构动力学、取向行为和阳离子残基的潜泳情况。结果表明，该肽的C端螺旋在所有六种模型双层中均得以保持，并且豹鳎毒素在DMPC、DPPC和POPG/POPE混合双层中的倾斜程度大于在POPC和POPG双层中的倾斜程度。此外，两性离子膜的结构比阴离子双层受该肽的影响更大。综上所述，该研究表明豹鳎毒素的阳离子残基向脂质双层界面潜泳，并且该肽的所有苯丙氨酸残基在肽-膜相互作用中发挥重要作用。我们希望这项工作将有助于更好地理解抗菌肽与膜的相互作用。
