title: Mechanism of a pH-induced peptide inserting into a POPC bilayer: a molecular dynamic study.
abstract: Membrane insertion peptides have been developed in recent years and serve as cargos to deliver small molecules into cells. A class of membrane insertion peptides is the so called pH-induced peptides (pHLIPs), which are able to insert into membrane when the environment pH is acidic. Despite a number of experimental studies, the insertion process as well as the penetration mechanism is still worth study with computational methods. Thus, we performed molecular dynamics simulations in this study to elucidate the detailed penetration process and mechanism. Both protonated and unprotonated peptides are employed to interact with a POPCs bilayer. By analyzing the trajectory of the simulation, the peptide travelling across membrane is expected to take milliseconds or seconds. While the peptide penetrating through the POPC bilayer boundary is much faster (several nanoseconds). More importantly, the elaborate energies between a peptide and water molecules, the energies between a peptide and POPCs have been analyzed throughout the simulation time correspondingly. A constant decrease of interaction energies have been observed for peptide-water interaction in the protonated condition. At last, we employ the statistics of hydrogen bonds to explain the penetration mechanism tentatively. For the protonated system, the decrease of hydrogen bonds of peptide-water and the increase of hydrogen bonds of peptide- POPCs have been considered as the main driven force for the peptide insertion.
authors.forename: Chui-Peng
authors.initials: CP
authors.lastname: Kong
authors.forename: Ying-Lu
authors.initials: YL
authors.lastname: Cui
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Zhang
authors.forename: Qing-Chuan
authors.initials: QC
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, People's Republic of China. zhanghx@jlu.edu.cn.
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Zhang
mesh_terms: D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D010713:Phosphatidylcholines; C533201:pHLIP protein; C028694:1-palmitoyl-2-oleoylphosphatidylcholine