Kabelka Ivo, Vácha Robert
National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
Faculty of Science and CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
J Chem Phys. 2015 Dec 28;143(24):243115. doi: 10.1063/1.4933229.
Amphiphilic peptides can interact with biological membranes and severely affect their barrier and signaling functions. These peptides, including antimicrobial peptides, can self-assemble into transmembrane pores that cause cell death. Despite their medical importance, the conditions required for pore formation remain elusive. Monte Carlo simulations with coarse-grained models enabled us to calculate the free energies of pore opening under various conditions. In agreement with oriented circular dichroism experiments, a high peptide-to-lipid ratio was found to be necessary for spontaneous pore assembly. The peptide length has a non-monotonic impact on pore formation, and the optimal length matches with the membrane thickness. Furthermore, the hydrophobicity of the peptide ends and the mutual positions of peptides on the membrane play a role.
两亲性肽可与生物膜相互作用，并严重影响其屏障和信号功能。这些肽，包括抗菌肽，可自组装成跨膜孔，导致细胞死亡。尽管它们在医学上很重要，但孔形成所需的条件仍然难以捉摸。使用粗粒度模型的蒙特卡罗模拟使我们能够计算各种条件下孔开放的自由能。与圆二色光谱实验一致，发现高肽-脂比是自发孔组装所必需的。肽的长度对孔形成有非单调影响，最佳长度与膜厚度相匹配。此外，肽末端的疏水性以及肽在膜上的相互位置也起作用。
