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.
Int J Mol Sci. 2013 Jul 12;14(7):14532-49. doi: 10.3390/ijms140714532.
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.
最近的功能机制研究实验报告称，一种 pH 低插入肽 (pHLIP) 可以在酸性 pH 下插入两性离子棕榈酰油酰基磷脂酰胆碱 (POPC) 脂质双层，同时在碱性 pH 下结合到双层表面。然而，pHLIP 与 POPC 双层之间 pH 依赖性相互作用的原子细节尚不清楚。在这项研究中，我们使用全原子分子动力学 (MD) 模拟，研究了 pHLIP 在酸性和碱性 pH 条件下与 POPC 双层的详细相互作用，这些条件与功能机制研究中使用的条件相同。模拟是通过采用初始配置来进行的，其中 pHLIP 被放置在水溶液中，与双层表面平行（系统 S）、部分插入（系统 P）或完全插入（系统 F）在 POPC 双层中。基于多次 200-ns MD 模拟，我们发现：1）在系统 S 中的 pHLIP 可以在酸性 pH 下自发插入 POPC 双层，而在碱性 pH 下结合到膜表面；2）在系统 P 中的 pHLIP 可以在酸性 pH 下深入插入 POPC 双层，而在碱性 pH 下它有离开的趋势，并停留在双层表面；3）在酸性 pH 下，系统 F 中的 pHLIP 保持α-螺旋结构，而在碱性 pH 下部分展开。这项研究提供了原子水平上 pHLIP 插入 POPC 双层的 pH 诱导作用。
