Accelerated molecular dynamics simulation analysis of MSI-594 in a lipid bilayer.
Accelerated molecular dynamics simulation analysis of MSI-594 in a lipid bilayer.
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脂质双层中MSI-594的加速分子动力学仿真分析。
DOI：
10.1039/c7cp01941f
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发表时间：
2017-07-26
期刊：
影响因子：
--
通讯作者：
Bhunia A
中科院分区：
文献类型：
--
作者：
Mukherjee S;Kar RK;Nanga RPR;Mroue KH;Ramamoorthy A;Bhunia A
对现有抗生素的多药耐药性是全球最具挑战性的威胁之一。在这方面，抗菌肽（AMPs）被认为是克服细菌耐药性的有效替代品之一。MSI-594是一种24残基线性α -螺旋阳离子AMP，已被证明通过地毯机制破坏细菌膜系统。为了更好地了解脂质组成对MSI-594功能的作用，本研究利用加速分子动力学（aMD）模拟研究了8种不同的模型膜系统。模拟结果有助于区分阳离子MSI-594对两性离子POPC、阴离子POPG和POPS以及中性POPE脂质部分的特殊影响。此外，还研究了各种非均相POPC/POPG（7:3）、POPC/POPS（7:3）和POPG/POPE（1:3和3:1）双层体系对MSI-594动态相互作用的影响。与肽相互作用对脂质双分子层的影响以脂质酰基链顺序、膜厚度以及酰基链动力学为特征。我们的模拟结果表明，脂质组成影响MSI-594的膜相互作用，表明膜选择性对其作用机制至关重要。本研究结果有助于获得MSI-594及其破膜抗菌作用机制的精确原子水平信息，以及设计下一代有效的抗菌肽。
Multidrug resistance against the existing antibiotics is one of the most challenging threats across the globe. Antimicrobial peptides (AMPs), in this regard, are considered to be one of the effective alternatives that can overcome bacterial resistance. MSI-594, a 24-residue linear alpha-helical cationic AMP, has been shown to function via carpet mechanism to disrupt the bacterial membrane systems. To better understand the role of lipid composition on the function of MSI-594, in the present study, eight different model membrane systems have been studied using accelerated molecular dynamics (aMD) simulation. The simulated results are helpful in discriminating the particular effects of cationic MSI-594 against zwitterionic POPC, anionic POPG and POPS, and neutral POPE lipid moieties. Additionally, the effects of various heterogeneous POPC/POPG (7:3), POPC/POPS (7:3), and POPG/POPE (1:3 and 3:1) bilayer systems on the dynamic interaction of MSI-594 have also been investigated. The effect on the lipid bilayer due to interaction with the peptide is characterized by lipid acyl-chain order, membrane thickness, as well as acyl-chain dynamics. Our simulation results show that the lipid composition affects the membrane interaction of MSI-594 suggesting that membrane selectivity is crucial to its mechanism of action. The resullts reported in this study are helpful to obtain accurate atomistic-level information governing MSI-594 and its membrane disruptive antimicrobial mechanism of action, as well as to design next generation potent antimicrobial peptides.
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影响因子：
4.6
作者：
Amos ST;Vermeer LS;Ferguson PM;Kozlowska J;Davy M;Bui TT;Drake AF;Lorenz CD;Mason AJ
通讯作者：
Mason AJ
影响因子：
3.4
作者：
Gullingsrud, J;Schulten, K
通讯作者：
Schulten, K
影响因子：
2.9
作者：
Lee, Dong-Kuk;Bhunia, Anirban;Ramamoorthy, Ayyalusamy
通讯作者：
Ramamoorthy, Ayyalusamy
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
影响因子：
5.8
作者：
Dahl, Anna Caroline E.;Chavent, Matthieu;Sansom, Mark S. P.
通讯作者：
Sansom, Mark S. P.