The molecular basis for the inhibitory action of a benzimidazole inhibitor compound to hepatitis C virus E1 envelope protein was examined computationally. Structures for the wild‐type E1 protein and seven mutants were modelled using an ab initio protein structure prediction algorithm, and these models were docked with the benzimidazole inhibitor. Top‐ranked conformers for each docked structure were examined in the context of the putative function of the inhibitor that blocks fusion of the envelope protein to the host cells. The results for the wild‐type protein and that for a series of mutants containing reported single, double and triple resistance mutations demonstrate that the inhibitor binds in the vicinity of residue Phe99 (at position 291 in the encoded polyprotein) at the C‐terminal end of a putative fusion domain. In so doing, the compound inhibits the virus from fusing to host cells and blocks viral replication in accord with the results from cell‐based infection studies.

中文翻译：

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苯并咪唑抑制剂对丙型肝炎病毒包膜糖蛋白的分子基础

通过计算检查了苯并咪唑抑制剂化合物对丙型肝炎病毒E1包膜蛋白的抑制作用的分子基础。使用从头算蛋白质结构预测算法对野生型E1蛋白和七个突变体的结构进行建模，并将这些模型与苯并咪唑抑制剂对接。在阻遏包膜蛋白与宿主细胞融合的抑制剂的推定功能的背景下，检查了每个停靠结构的最高构象异构体。野生型蛋白的结果以及一系列含有已报告的单，双和三抗突变的突变体的结果表明，该抑制剂在C末端的残基Phe99附近（在编码的多蛋白中的291位）结合。推定的融合结构域。这样，