Abbas Ghulam, Cardenas Alfredo E, Elber Ron
National Center for Bioinformatics, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Oden Institute for Computational and Engineering Sciences, University of Texas at Austin, Austin, TX 78712, USA.
Life (Basel). 2022 Sep 22;12(10):1473. doi: 10.3390/life12101473.
We conduct molecular dynamics simulations of model heterogeneous membranes and their interactions with a 24-amino acid peptide-NAF-1. NAF-1 is an anticancer peptide that selectively permeates and kills malignant cells; it does not permeate normal cells. We examine three membranes with different binary mixtures of lipids, DOPC-DOPA, DOPC-DOPS, and DOPC-DOPE, with a single peptide embedded in each as models for the diversity of biological membranes. We illustrate that the peptide organization in the membrane depends on the types of nearby phospholipids and is influenced by the charge and size of the head groups. The present study sheds light on early events of permeation and the mechanisms by which an amphiphilic peptide crosses from an aqueous solution to a hydrophobic membrane. Understanding the translocation mechanism is likely to help the design of new permeants.
我们对模型异质膜及其与一种24个氨基酸的肽——NAF-1的相互作用进行了分子动力学模拟。NAF-1是一种抗癌肽，它能选择性地渗透并杀死恶性细胞；它不会渗透正常细胞。我们研究了三种含有不同脂质二元混合物的膜，即二油酰磷脂酰胆碱-二油酰磷脂酸（DOPC-DOPA）、二油酰磷脂酰胆碱-二油酰磷脂丝氨酸（DOPC-DOPS）和二油酰磷脂酰胆碱-二油酰磷脂酰乙醇胺（DOPC-DOPE），每种膜中嵌入一个单一的肽，以此作为生物膜多样性的模型。我们阐明了膜中肽的组织方式取决于附近磷脂的类型，并受头部基团的电荷和大小影响。本研究揭示了渗透的早期事件以及两亲性肽从水溶液穿过到疏水膜的机制。了解转运机制可能有助于新型渗透剂的设计。
