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Membrane Binding and Insertion of a pHLIP Peptide Studied by All-Atom Molecular Dynamics Simulations
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
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
* Author to whom correspondence should be addressed.
Received: 31 May 2013; in revised form: 24 June 2013 / Accepted: 25 June 2013 / Published: 12 July 2013
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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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.
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.
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.