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Int. J. Mol. Sci. 2013, 14(7), 14532-14549; doi:10.3390/ijms140714532
Article

Membrane Binding and Insertion of a pHLIP Peptide Studied by All-Atom Molecular Dynamics Simulations

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 and
1,*
1 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 2 School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
* Author to whom correspondence should be addressed.
Received: 31 May 2013 / Revised: 24 June 2013 / Accepted: 25 June 2013 / Published: 12 July 2013
(This article belongs to the Special Issue Computational Modelling of Biological Membranes)
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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.
Keywords: pH low-insertion peptide (pHLIP); zwitterionic POPC; pH-triggered bilayer insertion; membrane binding; all-atom molecular dynamics simulations pH low-insertion peptide (pHLIP); zwitterionic POPC; pH-triggered bilayer insertion; membrane binding; all-atom molecular dynamics simulations
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Deng, Y.; Qian, Z.; Luo, Y.; Zhang, Y.; Mu, Y.; Wei, G. Membrane Binding and Insertion of a pHLIP Peptide Studied by All-Atom Molecular Dynamics Simulations. Int. J. Mol. Sci. 2013, 14, 14532-14549.

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