Sun Delin, Forsman Jan, Woodward Clifford E
School of Physical, Environmental and Mathematical Sciences, University of New South Wales , Canberra, ACT 2600, Australia.
Theoretical Chemistry, Chemical Centre, Lund University , P.O. Box 124, S-221 00 Lund, Sweden.
J Phys Chem B. 2017 Nov 9;121(44):10209-10214. doi: 10.1021/acs.jpcb.7b07126. Epub 2017 Oct 31.
Membrane-active peptides (MAPs) are able to induce pores in cell membranes via molecular mechanisms, which are still subject to ongoing research. In this work, we present molecular dynamics simulations that suggest a precursor membrane defect plays an important role in the pore-inducing activity of the prototypical antimicrobial peptide melittin. The simulations reveal that the hydrophobic N-terminus of melittin is able to recognize and insert into the membrane defect in the lipid bilayer and that this leads to a cascading transfer of adsorbed peptides to the membrane defect, leading to peptide aggregation in the pore. We show that this mechanism also acts in the case of a melittin mutant without the flexible central proline hinge, thus indicating the latter is not crucial to the activity of melittin, which is consistent with experiments.
膜活性肽（MAPs）能够通过分子机制在细胞膜上诱导形成孔道，而这些分子机制仍在研究之中。在这项工作中，我们进行了分子动力学模拟，结果表明前体膜缺陷在典型抗菌肽蜂毒肽的孔诱导活性中起着重要作用。模拟结果显示，蜂毒肽的疏水N端能够识别并插入脂质双分子层中的膜缺陷，这导致吸附的肽向膜缺陷进行级联转移，从而在孔道中形成肽聚集。我们发现，在没有柔性中央脯氨酸铰链的蜂毒肽突变体的情况下，这一机制同样起作用，因此表明后者对蜂毒肽的活性并非至关重要，这与实验结果一致。
