Liu Wen-long, Wang Lu-man, He Dong-qi, Zhang Tian-lan, Gou Bao-di, Li Qing
Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing, 100191,China.
Department of Applied Sciences, Peking University, Beijing, 100191, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2014 Oct 18;46(5):739-43.
To propose a calculation method of oligosaccharides' fractal dimension, and to provide a new approach to studying the drug molecular design and activity.
By using the principle of energy optimization and computer simulation technology, the steady structures of oligosaccharides were found, and an effective way of oligosaccharides fractal dimension's calculation was further established by applying the theory of box dimension to the chemical compounds.
By using the proposed method, 22 oligosaccharides' fractal dimensions were calculated, with the mean 1.518 8 ± 0.107 2; in addition, the fractal dimensions of the two activity multivalent oligosaccharides which were confirmed by experiments, An-2 and Gu-4, were about 1.478 8 and 1.516 0 respectively, while C-type lectin-like receptor Dectin-1's fractal dimension was about 1.541 2. The experimental and computational results were expected to help to find a class of glycoside drugs whose target receptor was Dectin-1.
Fractal dimension, differing from other known macro parameters, is a useful tool to characterize the compound molecules' microscopic structure and function, which may play an important role in the molecular design and biological activity study. In the process of oligosaccharides drug screening, the fractal dimension of receptor and designed oligosaccharides or glycoclusters can be calculated respectively. The oligosaccharides with fractal dimension close to that of target receptor should then take priority compared with others, to get the drug molecules with latent activity.
提出一种寡糖分形维数的计算方法，为药物分子设计与活性研究提供新途径。
利用能量优化原理和计算机模拟技术，寻找寡糖的稳定结构，并将盒维数理论应用于化合物，进一步建立寡糖分形维数的有效计算方法。
采用所提方法计算了22种寡糖的分形维数，均值为1.518 8±0.107 2；此外，实验证实的两种活性多价寡糖An-2和Gu-4的分形维数分别约为1.478 8和1.516 0，而C型凝集素样受体Dectin-1的分形维数约为1.541 2。实验与计算结果有望有助于找到一类以Dectin-1为靶受体的糖苷类药物。
分形维数不同于其他已知的宏观参数，是表征化合物分子微观结构和功能的有用工具，在分子设计和生物活性研究中可能发挥重要作用。在寡糖药物筛选过程中，可分别计算受体与设计的寡糖或糖簇的分形维数。与其他寡糖相比，分形维数与靶受体接近的寡糖应优先考虑，以获得具有潜在活性的药物分子。
