Analyses of the Binding between Water Soluble C60 Derivatives and Potential Drug Targets through a Molecular Docking Approach

Fullerene C60, a unique sphere-shaped molecule consisting of carbon, has been proved to have inhibitory effects on many diseases. However, the applications of C60 in medicine have been severely hindered by its complete insolubility in water and low solubility in almost all organic solvents. In this study, the water-soluble C60 derivatives and the C60 binding protein’s structures were collected from the literature. The selected proteins fall into several groups, including acetylcholinesterase, glutamate racemase, inosine monophosphate dehydrogenase, lumazine synthase, human estrogen receptor alpha, dihydrofolate reductase and N-myristoyltransferase. The C60 derivatives were docked into the binding sites in the proteins. The binding affinities of the C60 derivatives were calculated. The bindings between proteins and their known inhibitors or native ligands were also characterized in the same way. The results show that C60 derivatives form good interactions with the binding sites of different protein targets. In many cases, the binding affinities of C60 derivatives are better than those of known inhibitors and native ligands. This study demonstrates the interaction patterns of C60 derivatives and their binding partners, which will have good impact on the fullerene-based drug discovery.

富勒烯C60（Fullerene C60）是一种独特的球形碳基分子，现已被证实对多种疾病具有抑制作用。然而，由于其完全不溶于水、且在几乎所有有机溶剂中溶解度极低，C60在医学领域的应用受到了严重阻碍。本研究从已发表文献中收集了水溶性C60衍生物以及C60结合蛋白的结构信息。所筛选得到的蛋白可分为多个类别，包括乙酰胆碱酯酶、谷氨酸消旋酶、次黄嘌呤核苷酸脱氢酶、光黄素合酶（lumazine synthase）、人雌激素受体α、二氢叶酸还原酶以及N-肉豆蔻酰基转移酶。将C60衍生物分子对接至各蛋白的结合位点中，并计算其结合亲和力。同时，以相同方法表征了蛋白与其已知抑制剂或天然配体之间的结合作用。研究结果表明，C60衍生物可与不同蛋白靶点的结合位点形成良好的相互作用。在多数情况下，C60衍生物的结合亲和力优于已知抑制剂与天然配体。本研究阐明了C60衍生物与其结合伴侣的相互作用模式，将对基于富勒烯的药物开发产生积极影响。