抗菌肽是一类具有广谱杀菌作用的肽的总称，它们选择性地在微生物膜上形成跨膜通道来增加膜的通透性，从而实现抑菌或杀菌功能。它们形成的跨膜结构通常难以结晶，这为直接研究其抗菌机制带来了困难。
近期，物理与天文系和自然科学研究院的Jakob Ulmschneider、自然科学研究院的胡丹，以及约翰霍普金斯大学Martin Ulmschneider共同指导学生王昱焜和Charles Chen通过大规模分子动力学模拟结合验证性实验研究了一种抗菌肽Maculatin与生物膜的相互作用，其工作发表在Nature Communications。论文题目：Spontaneous formation of structurally diverse membrane channel architectures from a single antimicrobial peptide。
他们的工作表明，这类抗菌肽能通过多种自催化机制实现快速跨膜插入。同时，跨膜肽在膜上并非形成单一的稳定功能结构，而是形成多种处于动态平衡的跨膜聚合结构，其中只有处于高聚态（六聚体-八聚体）的结构具有完整的连续水通道，可以引起水和离子等细胞内容物的跨膜高速渗透，从而具有杀菌功能。他们的工作也为理解肽对膜的选择性以及生物分泌抗菌肽时避免自身毒性提供了思路。
A
bial peptides (AMPs) selectively target and form pores in microbial membranes. We report an experimentally guided unbiased simulation methodology that yields the mechanism of spontaneous pore assembly for the AMP maculatin at atomic resolution. Rather than a single pore, maculatin forms an ensemble of structurally diverse temporarily functional low-oligomeric pores, which mimic integral membrane protein channels in structure. These pores continuously form and dissociate in the membrane. Membrane permeabilization is dominated by hexa-, hepta-, and octomers, which conduct water, ions, and small dyes. Pores formed by consecutive addition of individual helices to a transmembrane helix or helix bundle, in contrast to current poration models. The diversity of the pore architectures – formed by a single sequence – may be a key feature in preventing self-toxicity and could explain why sequence-function relationships in AMPs remain elusive.
