title: Membrane binding and insertion of a pHLIP peptide studied by all-atom molecular dynamics simulations.
abstract: Recent experiments in function mechanism study reported that a pH low-insertion peptide (pHLIP) can insert into a zwitterionic palmitoyloleoylphosphatidylcholine (POPC) lipid bilayer at acidic pH while binding to the bilayer surface at basic pH. However, the atomic details of the pH-dependent interaction of pHLIP with a POPC bilayer are not well understood. In this study, we investigate the detailed interactions of pHLIP with a POPC bilayer at acidic and basic pH conditions as those used in function mechanism study, using all-atom molecular dynamics (MD) simulations. Simulations have been performed by employing the initial configurations, where pHLIP is placed in aqueous solution, parallel to bilayer surface (system S), partially-inserted (system P), or fully-inserted (system F) in POPC bilayers. On the basis of multiple 200-ns MD simulations, we found (1) pHLIP in system S can spontaneously insert into a POPC bilayer at acidic pH, while binding to the membrane surface at basic pH; (2) pHLIP in system P can insert deep into a POPC bilayer at acidic pH, while it has a tendency to exit, and stays at bilayer surface at basic pH; (3) pHLIP in system F keeps in an α-helical structure at acidic pH while partially unfolding at basic pH. This study provides at atomic-level the pH-induced insertion of pHLIP into POPC bilayer.
authors.affiliation: State Key Laboratory of Surface Physics, Key Laboratory for Computational Physical Sciences (Ministry of Education), and Department of Physics, Fudan University, 220 Handan Road, Shanghai 200433, China. 072019007@fudan.edu.cn
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Deng
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Qian
authors.forename: Yin
authors.initials: Y
authors.lastname: Luo
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Mu
authors.forename: Guanghong
authors.initials: G
authors.lastname: Wei
mesh_terms: D000595:Amino Acid Sequence; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry; D008051:Lipid Bilayers / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000737:chemistry; D011485:Protein Binding; D014867:Water / Q000737:chemistry
chemical_list: D007477:Ions; D008051:Lipid Bilayers; D008565:Membrane Proteins; D010713:Phosphatidylcholines; C533201:pHLIP protein; D014867:Water; C028694:1-palmitoyl-2-oleoylphosphatidylcholine