Department of Applied Mathematics, The University of Western Ontario, London, Ontario, Canada N6A 5B7.
J Phys Chem B. 2013 Jan 10;117(1):230-41. doi: 10.1021/jp310255r. Epub 2012 Dec 24.
Translocation of peptides through cellular membranes is a fundamental problem in developing antimicrobial peptides and in drug delivery. There is a class of peptides, known as cell-penetrating peptides, that are able to penetrate membranes without disrupting them. They can carry pharmacological compounds, thus a promising strategy for drug delivery. The physical mechanisms that facilitate translocation are not known. We have used large-scale molecular dynamics simulations to study the penetration of transportan across a zwitterionic dipalmitoyl-phosphatidyl-choline (DPPC) bilayer. We obtained the free energy profile for one peptide inside the bilayer and discuss the response of the bilayer to the presence of transportan. We also discuss the importance of lysine residues and speculate on the possible penetration mechanism of the peptide and propose a graded-like penetration process.
跨细胞膜的肽转运是开发抗菌肽和药物传递的一个基本问题。有一类被称为穿透肽的肽能够穿透细胞膜而不破坏它们。它们可以携带药理化合物，因此是一种很有前途的药物传递策略。促进转运的物理机制尚不清楚。我们使用大规模的分子动力学模拟来研究转运肽在两性离子二棕榈酰磷脂酰胆碱 (DPPC) 双层中的穿透。我们得到了一个肽在双层内的自由能分布，并讨论了双层对转运肽存在的响应。我们还讨论了赖氨酸残基的重要性，并推测了肽的可能穿透机制，并提出了一个分级样的穿透过程。
