多肽柔韧性和疏水力矩是评价抗肽肽临床潜力的决定因素。

IF 2.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Journal of Membrane Biology Pub Date : 2023-12-01 Epub Date: 2023-04-25 DOI:10.1007/s00232-023-00286-w
Daniel Balleza
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引用次数: 0

摘要

利用柔性预测算法和计算机结构建模,我们计算了几种magainin导数的固有柔性。在magainin-2 (Mag-2)和magainin H2 (MAG-H2)的情况下,我们发现Mag-2比它的疏水类似物MAG-H2更灵活。这影响了两种肽的弯曲程度,在两个中心残基(R10, R11)周围发生扭结,而在Mag-H2中,W10使肽变硬。此外,这增加了Mag-H2的疏水力矩,这可以解释它在POPC模型膜上形成孔的倾向,其自发曲率接近于零。同样,DOPC膜中描述的这种肽促进孔隙形成的保护作用可能与这种脂质形成负自发曲率膜的倾向有关。另一种磁力模拟(MSI-78)的灵活性甚至比磁力-2更大。这使得肽在中心F12周围呈现出一种铰链,以及一个易于无序的c端。这些特征是了解该肽所表现出的广谱抗菌作用的关键。这些数据加强了自发膜曲率、内在肽柔韧性和特定疏水力矩在评估膜活性抗菌肽生物活性中的决定作用的假设。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Peptide Flexibility and the Hydrophobic Moment are Determinants to Evaluate the Clinical Potential of Magainins.

Peptide Flexibility and the Hydrophobic Moment are Determinants to Evaluate the Clinical Potential of Magainins.

Using a flexibility prediction algorithm and in silico structural modeling, we have calculated the intrinsic flexibility of several magainin derivatives. In the case of magainin-2 (Mag-2) and magainin H2 (MAG-H2) we have found that MAG-2 is more flexible than its hydrophobic analog, Mag-H2. This affects the degree of bending of both peptides, with a kink around two central residues (R10, R11), whereas, in Mag-H2, W10 stiffens the peptide. Moreover, this increases the hydrophobic moment of Mag-H2, which could explain its propensity to form pores in POPC model membranes, which exhibit near-to-zero spontaneous curvatures. Likewise, the protective effect described in DOPC membranes for this peptide regarding its facilitation in pore formation would be related to the propensity of this lipid to form membranes with negative spontaneous curvature. The flexibility of another magainin analog (MSI-78) is even greater than that of Mag-2. This facilitates the peptide to present a kind of hinge around the central F12 as well as a C-terminal end prone to be disordered. Such characteristics are key to understanding the broad-spectrum antimicrobial actions exhibited by this peptide. These data reinforce the hypothesis on the determinant role of spontaneous membrane curvature, intrinsic peptide flexibility, and specific hydrophobic moment in assessing the bioactivity of membrane-active antimicrobial peptides.

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来源期刊
Journal of Membrane Biology
Journal of Membrane Biology 生物-生化与分子生物学
CiteScore
4.80
自引率
4.20%
发文量
63
审稿时长
6-12 weeks
期刊介绍: The Journal of Membrane Biology is dedicated to publishing high-quality science related to membrane biology, biochemistry and biophysics. In particular, we welcome work that uses modern experimental or computational methods including but not limited to those with microscopy, diffraction, NMR, computer simulations, or biochemistry aimed at membrane associated or membrane embedded proteins or model membrane systems. These methods might be applied to study topics like membrane protein structure and function, membrane mediated or controlled signaling mechanisms, cell-cell communication via gap junctions, the behavior of proteins and lipids based on monolayer or bilayer systems, or genetic and regulatory mechanisms controlling membrane function. Research articles, short communications and reviews are all welcome. We also encourage authors to consider publishing ''negative'' results where experiments or simulations were well performed, but resulted in unusual or unexpected outcomes without obvious explanations. While we welcome connections to clinical studies, submissions that are primarily clinical in nature or that fail to make connections to the basic science issues of membrane structure, chemistry and function, are not appropriate for the journal. In a similar way, studies that are primarily descriptive and narratives of assays in a clinical or population study are best published in other journals. If you are not certain, it is entirely appropriate to write to us to inquire if your study is a good fit for the journal.
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