title: Early stages of interactions of cell-penetrating peptide penetratin with a DPPC bilayer.
abstract: Cell-penetrating-peptides (CPPs) can deliver themselves together with a macromolecular cargo into cells and, hence, have promising applications in drug delivery. The detailed physical mechanisms that underlie and determine their cellular uptake remain unknown. We used molecular dynamics (MD) simulations to study the interaction of a well-known CPP, namely penetratin, with a zwitterionic di-palmitoyl-phosphatidyl-choline (DPPC) bilayer. Our study shows that the arginine and lysine residues play a crucial role in peptide-membrane binding through charge-pair and hydrogen bond interactions. We also characterize peptide conformation and show that it remains helical near the N-terminus but can fold into a variety of other conformations in the residues close to the C-terminus. The response of membrane to the peptide is also investigated.
authors.affiliation: Department of Applied Mathematics, The University of Western Ontario, London, ON, Canada N6A 5B7.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Pourmousa
authors.forename: Mikko
authors.initials: M
authors.lastname: Karttunen
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D016062:Porosity; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D008051:Lipid Bilayers; D015060:1,2-Dipalmitoylphosphatidylcholine; C414409:penetratin