Membrane binding and insertion of a pHLIP peptide studied by all-atom molecular dynamics simulations.
Membrane binding and insertion of a pHLIP peptide studied by all-atom molecular dynamics simulations.
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DOI：
10.3390/ijms140714532
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发表时间：
2013-07-12
影响因子：
5.6
通讯作者：
Wei G
中科院分区：
文献类型：
--
作者：
Deng Y;Qian Z;Luo Y;Zhang Y;Mu Y;Wei G
近期在功能机制研究方面的实验报道称，一种pH低插入肽（pHLIP）在酸性pH值下能够插入到两性离子的棕榈酰油酰磷脂酰胆碱（POPC）脂质双层中，而在碱性pH值下则结合在双层表面。然而，pHLIP与POPC双层之间这种依赖pH的相互作用的原子细节尚未被充分了解。在本研究中，我们利用全原子分子动力学（MD）模拟，研究了在功能机制研究中所使用的酸性和碱性pH条件下pHLIP与POPC双层的详细相互作用。模拟是通过采用初始构型进行的，其中pHLIP被置于水溶液中，与双层表面平行（体系S）、部分插入（体系P）或完全插入（体系F）到POPC双层中。基于多次200纳秒的MD模拟，我们发现：（1）体系S中的pHLIP在酸性pH值下能够自发地插入到POPC双层中，而在碱性pH值下结合在膜表面；（2）体系P中的pHLIP在酸性pH值下能够深入插入到POPC双层中，而在碱性pH值下它有退出的趋势，并停留在双层表面；（3）体系F中的pHLIP在酸性pH值下保持α - 螺旋结构，而在碱性pH值下部分展开。本研究在原子水平上揭示了pH诱导的pHLIP插入POPC双层的过程。
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.
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影响因子：
3.7
作者：
Duan M;Fan J;Huo S
通讯作者：
Huo S
影响因子：
3.4
作者：
Hoff, B;Strandberg, E;Posten, C
通讯作者：
Posten, C
影响因子：
2.4
作者：
Kucerka, N;Tristram-Nagle, S;Nagle, JF
通讯作者：
Nagle, JF
DOI：
10.1073/pnas.0914330107
发表时间：
2010-03-02
影响因子：
11.1
作者：
Andreev, Oleg A.;Karabadzhak, Alexander G.;Reshetnyak, Yana K.
通讯作者：
Reshetnyak, Yana K.
影响因子：
5.5
作者：
Piccinini, Enrico;Ceccarelli, Matteo;Jacoboni, Carlo
通讯作者：
Jacoboni, Carlo