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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Received: 31 May 2013; in revised form: 24 June 2013 / Accepted: 25 June 2013 / Published: 12 July 2013
(This article belongs to the Special Issue Computational Modelling of Biological Membranes)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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
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MDPI and ACS Style

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.

AMA Style

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. International Journal of Molecular Sciences. 2013; 14(7):14532-14549.

Chicago/Turabian Style

Deng, Yonghua; Qian, Zhenyu; Luo, Yin; Zhang, Yun; Mu, Yuguang; Wei, Guanghong. 2013. "Membrane Binding and Insertion of a pHLIP Peptide Studied by All-Atom Molecular Dynamics Simulations." Int. J. Mol. Sci. 14, no. 7: 14532-14549.

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