Molecular Dynamics Investigation into the Effect of Zinc(II) on the Structure and Membrane Interactions of the Antimicrobial Peptide Clavanin A
Molecular Dynamics Investigation into the Effect of Zinc(II) on the Structure and Membrane Interactions of the Antimicrobial Peptide Clavanin A
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DOI：
10.1021/acs.jpcb.8b11496
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发表时间：
2019-04-18
影响因子：
3.3
通讯作者：
May, Eric R.
中科院分区：
文献类型：
--
作者：
Duay, Searle S.;Sharma, Gaurav;May, Eric R.
Clavanin A （ClavA）是一种抗菌肽（AMP），其抗菌活性在Zn（II）离子存在下增强。在Zn（II）离子存在下，ClavA的抗菌活性提高了16倍。在这项研究中，我们研究了这种增强的潜在来源，即锌（II）结合对ClavA螺旋构象的影响，以及对ClavA与革兰氏阴性细菌膜模型相互作用的影响。此外，我们还研究了锌（II）对膜力学性能的影响。我们采用了ClavA全螺旋和随机螺旋结构的全原子平衡分子动力学模拟。我们观察到Zn（II）可以稳定Zn（II）结合区内现有的螺旋构象，但我们没有观察到在随机线圈结构中启动的系统中诱导螺旋构象。Zn（II）与ClavA的结合为c端膜结合提供了更有利的静电。这是由更长和更强的c端脂质相互作用证明的。锌（II）也能够以一种有利于ClavA插入和增强转运到细胞中的潜力的方式调节膜的特性。这项工作提供了深入了解二价金属阳离子在ClavA抗菌活性中的作用。该信息可用于开发含有可结合金属基序的合成AMPs（金属AMPs），用于治疗和医疗目的。
Clavanin A (ClavA) is an antimicrobial peptide (AMP) whose antimicrobial activity is enhanced in the presence of Zn(II) ions. The antimicrobial activity of ClavA has been shown to increase 16-fold in the presence of Zn(II) ions. In this study, we investigate the potential sources of this enhancement, namely, the effect of Zn(II) binding on the helical conformation of ClavA and on the ClavA interaction with a model for gram-negative bacterial membranes. In addition, we investigate the effect of Zn(II) on the membrane mechanical properties. We employed all-atom equilibrium molecular dynamics simulations initiated from both fully helical and random coil structures of ClavA. We observe that Zn(II) can stabilize an existing helical conformation in the Zn(II)-binding region, but we do not observe induction of helical conformations in systems initiated in random coil configurations. Zn(II) binding to ClavA provides more favorable electrostatics for membrane association in the C-terminal region. This is evidenced by longer and stronger C-terminal-lipid interactions. Zn(II) is also capable of modulating the membrane properties in a manner which favors ClavA insertion and the potential for enhanced translocation into the cell. This work provides insights into the role of divalent metal cations in the antimicrobial activity of ClavA. This information can be used for the development of synthetic AMPs containing motifs that can bind metals (metalloAMPs) for therapeutic and medical purposes.