Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
Department of Computer engineering, Faculty of Engineering, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand.
Comput Biol Chem. 2019 Dec;83:107091. doi: 10.1016/j.compbiolchem.2019.107091. Epub 2019 Jul 13.
Human α -defensin 5 (HD5) is a 32-residue cysteine-rich host-defense peptide that exhibits broad-spectrum antimicrobial activity and plays an essential role in innate immunity in the human gut and other organ systems. Although its antimicrobial mechanism of action remains unclear, the high salt concentration seems to attenuate the antimicrobial function of HD5 via an unknown mechanism. In this work, we employ Molecular Dynamics (MD) simulations to analyse the oligomerization behaviour of HD5 when exposed to different salt concentration. We demonstrate that the presence of salt, such as sodium chloride (NaCl), promotes HD5 to form higher-order oligomers (up to heptamers) in our simulations. In addition, we also analyse the electrostatic interactions between the two Glu residues (E14 and E21) and their neighbouring residues. Our data confirm that the E14 residue is essential for the structural integrity, whereas the E21 residue contributes to the dimerization of HD5, suggesting that these Glu residues are important for the antimicrobial function of this peptide.
人α-防御素 5 (HD5) 是一种含有 32 个残基的富含半胱氨酸的宿主防御肽，具有广谱抗菌活性，在人体肠道和其他器官系统的先天免疫中发挥着重要作用。尽管其抗菌作用机制尚不清楚，但高盐浓度似乎通过未知机制减弱了 HD5 的抗菌功能。在这项工作中，我们采用分子动力学 (MD) 模拟来分析暴露在不同盐浓度下 HD5 的寡聚行为。我们证明，盐（如氯化钠 (NaCl)）的存在会促进 HD5 在模拟中形成更高阶的寡聚物（高达七聚体）。此外，我们还分析了两个 Glu 残基 (E14 和 E21) 及其相邻残基之间的静电相互作用。我们的数据证实 E14 残基对于结构完整性至关重要，而 E21 残基有助于 HD5 的二聚化，这表明这些 Glu 残基对于该肽的抗菌功能很重要。
