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通过比较天然血红素蛋白中血红素与多肽链进行共价连接的结构,我们对组氨酸(His)或二肽半胱氨酰-组氨酸(Cys-His)共价修饰人工配合物Fe(III)-salophen进行了计算机模拟,旨在为设计包含非天然辅基的金属蛋白分子提供有用的信息。修饰物采用分子力学MM+方法进行了分子构型优化,而且在最低能量构型的基础上,采用半经验量子化学ZINDO/1方法进行了单点计算。结果阐明,当His形成Fe(III)-salophen的第五轴向配体时,通过与His形成酰胺键进行共价修饰,引入丙酸根要比甲酸根使分子更加稳定;同时,在Fe(III)-salophem的位置a进行His或Cys-His共价修饰,均比在位置b进行修饰使分子更加稳定。此外,在所有修饰物分子中,最稳定的分子为:通过Cys与a位置所引入的乙烯基之间形成硫醚键的二肽Cys-His修饰物。这一结构与自然界中c型细胞色素一致。本研究提供了一些初步的理论研究结果,它能够指导功能性Fe(III)-salophen配合物的构建以及在人工金属蛋白设计中的应用。
By comparing the structures of covalently linked heme to polypeptide chains in native heme proteins, we covalently modified the complex Fe (His) or dipeptide cys-His (Cys-His) (III) -salophen was computer-aided to provide useful information for the design of metalloprotein molecules that contain non-native prosthetic groups. The modifiers were optimized by molecular mechanics MM + method. Based on the lowest energy conformation, the semi-empirical quantum chemistry ZINDO / 1 method was used for single point calculation. The results show that when His forms the fifth axial ligand of Fe (III) -salophen, the introduction of propionate is more stable than the formate by covalent modification with His formed amide bond. Meanwhile, ) -salophem at position a for either His or Cys-His covalently, both being more stable than the modification at position b. In addition, the most stable molecule among all modifier molecules is the dipeptide Cys-His modification that forms a thioether bond between the Cys and the vinyl group introduced at the a position. This structure is in line with c-type cytochromes in nature. This study provides some preliminary theoretical results, which can guide the construction of functional Fe (III) -salophen complexes and their applications in the design of artificial metalloproteinases.