寡糖分子结构及其分形

Molecular structure and fractal analysis of oligosaccharide

目的:提出一种计算寡糖分子结构分形维数的有效方法,为寡糖药物的分子设计及活性研究提供新的思路。方法:利用能量优化原理和计算机模拟技术,找到寡糖分子的稳态位型,进一步应用分形理论的盒维数原理,建立一种计算寡糖分形维数的有效方法。结果:应用所提出的方法,计算得到22种寡糖的分形维数,其均值m=1.518 8±0.107 2。此外,经实验证实有活性的多价寡糖An-2和Gu-4分形维数分别为1.478 1和1.516 0,而C型凝集素样受体Dectin-1的受体结合域2CL8的分形维数为1.541 2。实验和计算结果有助于发现一类以Dectin-1为受体的糖苷类药物。结论:分形维数是能够区别于其他已知宏观参量而表征化合物分子微观结构和功能的参量,在寡糖药物的分子设计及活性研究中可能发挥重要作用。做寡糖药物筛选时,可先分别计算受体及所设计寡糖或糖簇分子的分形维数,而后选择分形维数相接近的进行合成,以期得到具有潜在活性的药物分子。

Objective：To propose a calculation method of oligosaccharides＇ fractal dimension,and to provide a new approach to studying the drug molecular design and activity. Methods： 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. Results： 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.Conclusion： 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.