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首页> 外文期刊>Biochimica et biophysica acta. Biomembranes >Binding, folding and insertion of a beta-hairpin peptide at a lipid bilayer surface: Influence of electrostatics and lipid tail packing
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Binding, folding and insertion of a beta-hairpin peptide at a lipid bilayer surface: Influence of electrostatics and lipid tail packing

机译：在脂质双层表面上的β-发夹肽的粘合，折叠和插入：静电和脂尾填料的影响

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摘要

Antimicrobial peptides (AMPs) act as host defenses against microbial pathogens. Here we investigate the interactions of SVS-1 (INKVICVICV PTTKVKVKVK), an engineered AMP and anti-cancer beta-hairpin peptide, with lipid bilayers using spectroscopic studies and atomistic molecular dynamics simulations. In agreement with literature reports, simulation and experiment show preferential binding of SVS-1 peptides to anionic over neutral bilayers. Fluorescence and circular dichroism studies of a Trp-substituted SVS-1 analogue indicate, however, that it will bind to a zwitterionic DPPC bilayer under high-curvature conditions and folds into a hairpin. In bilayers formed from a 1:1 mixture of DPPC and anionic DPPG lipids, curvature and lipid fluidity are also observed to promote deeper insertion of the fluorescent peptide. Simulations using the CHARMM C36m force field offer complementary insight into timescales and mechanisms of folding and insertion. SVS-1 simulated dt an anionic mixed POPC/POPG bilayer folded into a hairpin over a microsecond, the final stage in folding coinciding with the establishment of contact between the peptide's valine sidechains and the lipid tails through a "flip and dip" mechanism. Partial, transient folding and superficial bilayer contact are seen in simulation of the peptide at a zwitterionic POPC bilayer. Only when external surface tension is applied does the peptide establish lasting contact with the POPC bilayer. Our findings reveal the influence of disruption to lipid headgroup packing (via curvature or surface tension) on the pathway of binding and insertion, highlighting the collaborative effort of electrostatic and hydrophobic interactions on interaction of SVS-1 with lipid bilayers.
机译：抗微生物肽（AMPS）充当针对微生物病原体的宿主防御。在这里，我们研究了使用光谱研究和原子分子动力学模拟的脂质双层的SVS-1（InkVICVICV PTTKVKVKVKVK），工程放大器和抗癌β-发夹肽的相互作用。同意文献报告，模拟和实验表明SVS-1肽对中性双层的阴离子的优先结合。然而，TRP取代的SVS-1-1类似物的荧光和圆形二色性研究表明，它将在高曲率条件下与两性离子DPPC双层结合，并将其折叠成牵引力。在由1：1的DPPC和阴离子DPPG脂质的混合物形成的双层中，还观察到曲率和脂质流动性以促进荧光肽的更深插入。使用CHARMM C36M Force Field的模拟提供互补的洞察时间表和折叠和插入机制。 SVS-1模拟DT将阴离子混合POPC / POPG双层折叠成牵引成牵引，在折叠的最后阶段与肽的缬氨酸侧链和脂尾气之间的建立相吻合，通过“翻转和浸”机构。部分，瞬态折叠和浅表双层接触是在两性离子缺口双层的肽的模拟中。只有当施加外表面张力时，肽才能与POPC双层建立持久的接触。我们的研究结果揭示了破坏对脂质头组填料（通过曲率或表面张力）对结合和插入途径的影响，突出了静电和疏水相互作用与脂质双层的SVS-1相互作用的协作努力。

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