氨基酸His或二肽Cys-His共价修饰Fe(Ⅲ)-salophen的计算机模拟(英文)

Simulating the covalent modification of Fe(III)-salophen with amino acid histidine or dipeptide Cys-His

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。

Comparing with the structure of heme group that covalently linked to the polypeptide chain in natural heme proteins, we simulated the covalent modification of artificial Fe(III)-salophen complex with amino acid histidine (His) or dipeptide cysteinyl-histidine (Cys-His), with the intention of providing useful information for design of metalloproteins containing nonnatural prosthetic group. By using molecular mechanics MM+ method, the molecular geometries were optimized, and then the single point calculation was carried out on the obtained structure with minimum energy by using semi-empirical ZINDO/1 method. Results illustrate that, with His serving as the fifth ligand of Fe(III)-salophen, the molecule would be more stable when it was modified covalently, through forming an amide bond with His, by introducing a propionic group rather than a formic group. At the same time, the molecule would be more stable as modification occurred at position a rather than b of Fe(III)-salophen, for both cases of His and Cys-His modification. In addition, of all these modified complexes, the most stable molecule was that being modified with dipeptide Cys-His at position a through a thioether bond that formed between the cysteine residue and an introduced vinyl group. This conformation consists with that found in natural c-type cytochromes. The current study presents the initial theoretical results, which could instruct the successful construction of functional Fe(HI)-salophen complex, and also direct its application in artificial metalloproteins design.