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

• Main Authors: Guanghong Wei, Yuguang Mu, Yun Zhang, Yin Luo, Zhenyu Qian, Yonghua Deng
• Format: Article
• Language: English
• Published: MDPI AG 2013-07-01
• Series: International Journal of Molecular Sciences
• Subjects: pH low-insertion peptide (pHLIP); zwitterionic POPC; pH-triggered bilayer insertion; membrane binding; all-atom molecular dynamics simulations
• Online Access: http://www.mdpi.com/1422-0067/14/7/14532

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.