In silico investigations of possible routes of assembly of ORF 3a from SARS-CoV.
In silico investigations of possible routes of assembly of ORF 3a from SARS-CoV.
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DOI：
10.1007/s00894-011-1092-6
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发表时间：
2012-02
影响因子：
2.2
通讯作者：
Fischer WB
中科院分区：
文献类型：
--
作者：
Hsu HJ;Fischer WB
人传染性非典型肺炎冠状病毒(SARS-CoV)ORF3a是由274个氨基酸残基组成的膜蛋白。当这种蛋白在非洲爪哇卵母细胞中表达时，就会形成通道。基于生物信息学的方法，已经确定该拓扑结构包括三个跨膜结构域(TMD)。由于仍然缺乏来自实验的结构模型，因此可以挑战计算方法来生成这样的模型。在这项研究中，提出了一种顺序组装的方法，即一个接一个地组装单个TMD。将该协议与同时组装所有TMD的协调协议进行了比较。研究了在单体组装成束的过程中TMD之间的环的作用。分子动力学模拟作为短期平衡进行了20秒，以评估脂类环境中的束稳定性。结果表明，第二个TMD可能朝向推定的孔隙。所有推测的纤维束都显示，水分子被困在毛孔的管腔内，只有偶尔发生完全交叉的事件。本文的在线版本(doi：10.1007/s00894-0111092-6)包含补充材料，可供授权用户使用。
ORF 3a of human severe acute respiratory syndrome corona virus (SARS-CoV) has been identified as a 274 amino acid membrane protein. When expressed in Xenopus oocytes the protein forms channels. Based on bioinformatics approaches the topology has been identified to include three transmembrane domains (TMDs). Since structural models from experiments are still lacking, computational methods can be challenged to generate such models. In this study, a ‘sequential approach’ for the assembly is proposed in which the individual TMDs are assembled one by one. This protocol is compared with a concerted protocol in which all TMDs are assembled simultaneously. The role of the loops between the TMDs during assembly of the monomers into a bundle is investigated. Molecular dynamics simulations for 20 ns are performed as a short equilibration to assess the bundle stability in a lipid environment. The results suggest that bundles are likely with the second TMD facing the putative pore. All the putative bundles show water molecules trapped within the lumen of the pore with only occasional events of complete crossing. The online version of this article (doi:10.1007/s00894-011-1092-6) contains supplementary material, which is available to authorized users.
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DOI：
10.1016/j.bbamem.2010.05.014
发表时间：
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期刊：
Biochimica et biophysica acta
影响因子：
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作者：
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DOI：
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发表时间：
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影响因子：
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