论文标题
流感A，B M2和MERS- SARS-COV E病毒蛋白的跨膜肽的折叠分子动力学模拟
Folding Molecular Dynamics Simulations of the Transmembrane Peptides of Influenza A, B M2, and MERS-, SARS-CoV E Viral Proteins
论文作者
论文摘要
病毒蛋白是在宿主细胞的膜中寡聚并诱导这些膜中亲水性孔的形成，从而改变宿主细胞的生理特性，从而改变了宿主细胞的膜，并诱导亲亲水性孔的形成。由于它们对病毒致病性的重要性，它们已成为药物干预的靶标，尤其是通过阻断其形成孔隙活性的化合物。在这里，我们通过研究和比较（通过分子动力学模拟）来添加有关蛋白质蛋白的结构和功能的越来越多的文献，它衍生自四个病毒的跨膜肽的跨膜结构肽的折叠：流感A，流感B和Coronaviruses Mers-Mers-Cov-2-2和Sars-Cov-2和Sars-Cov-2。通过在显式溶剂（TFE）中总共超过50μs的仿真时间，并具有完整的静电，我们表征了这些跨膜肽的折叠行为，螺旋稳定性和螺旋倾向，并且我们可以确定可能反映其Quaternary组织和//生物学功能的常见基序。 We show that the two influenza-derived peptides are significantly different in peptide sequence and secondary structure from the two coronavirus-derived peptides, and that they are organized in two structurally distinct parts : a significantly more stable N-terminal half, and a fast converting C-terminal half that continuously folds and unfolds between $α$-helical structures and non-canonical structures which are mostly turns.相比之下，与流感的两种冠状病毒衍生的跨膜肽相比，跨膜肽更稳定，快速螺旋形成器。我们讨论了这些发现的可能解释及其与各自的Viroporins结构特征的推定联系。
Viroporins are small viral proteins that oligomerize in the membrane of host cells and induce the formation of hydrophilic pores in these membranes, thus altering the physiological properties of the host cells. Due to their significance for viral pathogenicity, they have become targets for pharmaceutical intervention, especially through compounds that block their pore-forming activity. Here we add to the growing literature concerning the structure and function of viroporins by studying and comparing -- through molecular dynamics simulations -- the folding of the transmembrane domain peptides of viroporins derived from four viruses : influenza A, influenza B, and the coronaviruses MERS-Cov-2 and SARS-CoV-2. Through a total of more than 50 μs of simulation time in explicit solvent (TFE) and with full electrostatics, we characterize the folding behavior, helical stability and helical propensity of these transmembrane peptides in their monomeric state and we identify common motifs that may reflect their quaternary organization and/or biological function. We show that the two influenza-derived peptides are significantly different in peptide sequence and secondary structure from the two coronavirus-derived peptides, and that they are organized in two structurally distinct parts : a significantly more stable N-terminal half, and a fast converting C-terminal half that continuously folds and unfolds between $α$-helical structures and non-canonical structures which are mostly turns. In contrast, the two coronavirus-derived transmembrane peptides are much more stable and fast helix formers when compared with the influenza ones. We discuss possible interpretations of these findings and their putative connection to the structural characteristics of the respective viroporins.
