Best of Two Worlds? How MD Simulations of Amphiphilic Helical Peptides in Membranes Can Complement Data from Oriented Solid-State NMR.
Best of Two Worlds? How MD Simulations of Amphiphilic Helical Peptides in Membranes Can Complement Data from Oriented Solid-State NMR.
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DOI：
10.1021/acs.jctc.8b00283
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发表时间：
2018-10
影响因子：
5.5
通讯作者：
S. Reißer;E. Strandberg;T. Steinbrecher;M. Elstner;A. Ulrich
中科院分区：
文献类型：
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作者：
S. Reißer;E. Strandberg;T. Steinbrecher;M. Elstner;A. Ulrich
通过将四极分裂拟合到理想的α-螺旋，可以从固态2 H NMR中获得取向磷脂双层中螺旋两亲肽的膜排列的整体和时间平均值。与此同时，分子动力学（MD）模拟可以提供原子洞察肽膜系统。在这里，我们评估MD模拟的潜力，以补充实验NMR数据，可在三个示例性的系统：天然抗菌肽PGLa和两个设计师制作的肽MSI-103和KIA 14，其序列来自PGLa。每种肽在DMPC脂质双层中模拟1 μs。我们从MD模拟中计算出了定义相对于肽螺旋的侧链几何形状的局部角度。然后（i）直接从模拟计算，（ii）从反算MD衍生的NMR分裂计算，和（iii）从实验2 H NMR分裂计算肽取向。我们的发现是：（1）在NMR分析中发现的肽的膜取向和二级结构通常被模拟很好地再现：（2）相对于螺旋骨架的侧链的几何形状可以明显偏离理想结构，这取决于特定的残基，但平均而言，所有侧链具有相同的取向;（3）对于我们所有的肽，从MD衍生的分裂中发现的方位旋转角比实验值小约15°。
The membrane alignment of helical amphiphilic peptides in oriented phospholipid bilayers can be obtained as ensemble and time averages from solid state 2H NMR by fitting the quadrupolar splittings to ideal α-helices. At the same time, molecular dynamics (MD) simulations can provide atomistic insight into peptide-membrane systems. Here, we evaluate the potential of MD simulations to complement the experimental NMR data that is available on three exemplary systems: the natural antimicrobial peptide PGLa and the two designer-made peptides MSI-103 and KIA14, whose sequences were derived from PGLa. Each peptide was simulated for 1 μs in a DMPC lipid bilayer. We calculated from the MD simulations the local angles which define the side chain geometry with respect to the peptide helix. The peptide orientation was then calculated (i) directly from the simulation, (ii) from back-calculated MD-derived NMR splittings, and (iii) from experimental 2H NMR splittings. Our findings are that (1) the membrane orientation and secondary structure of the peptides found in the NMR analysis are generally well reproduced by the simulations; (2) the geometry of the side chains with respect to the helix backbone can deviate significantly from the ideal structure depending on the specific residue, but on average all side chains have the same orientation; and (3) for all of our peptides, the azimuthal rotation angle found from the MD-derived splittings is about 15° smaller than the experimental value.