Lopez Carlos F, Nielsen Steve O, Moore Preston B, Klein Michael L
Center for Molecular Modeling, Chemistry Department, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104-6323, USA.
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4431-4. doi: 10.1073/pnas.0400352101. Epub 2004 Mar 12.
Synthetic and natural peptide assemblies can possess transport or conductance activity across biomembranes through the formation of nanopores. The fundamental mechanisms of membrane insertion necessary for antimicrobial or synthetic pore formation are poorly understood. We observe a lipid-assisted mechanism for passive insertion into a model membrane from molecular dynamics simulations. The assembly used in the study, a generic nanotube functionalized with hydrophilic termini, is assisted in crossing the membrane core by transleaflet lipid flips. Lipid tails occlude a purely hydrophobic nanotube. The observed insertion mechanism requirements for hydrophobic-hydrophilic matching have implications for the design of synthetic channels and antibiotics.
合成肽和天然肽组装体可通过形成纳米孔而具有跨生物膜的转运或传导活性。对抗菌或合成孔形成所必需的膜插入基本机制了解甚少。我们通过分子动力学模拟观察到一种脂质辅助的被动插入模型膜的机制。该研究中使用的组装体是一种带有亲水性末端功能化的通用纳米管，通过跨膜脂质翻转辅助其穿过膜核心。脂质尾部封闭了一个纯疏水的纳米管。观察到的疏水-亲水匹配的插入机制要求对合成通道和抗生素的设计具有启示意义。
