Under the guidance of the targeted molecules, brain-targeted liposomes can carry drugs quickly through the blood-brain barrier to achieve the target enrichment of drugs in the brain, so the design of the target molecules is the key to the preparation of high-efficiency brain targeted liposomes. In this study, SYBYL-X2.1.1 software was used to study the number and connection mode of each segment structure (glucose segment, fatty-chain and cholesterol segment) in the design of targeted molecular structure. GROMACS is used for calculation of molecular dynamics simulation, and G_MMPBSA is used for calculation of binding free energy. The results showed that glucose molecules interacted with 4PYP through hydrogen bond and Van der Waals forces. The amount of glucose in the glucoside molecule and the length of the fatty-chain had a significant effect on the interaction between the molecule and 4PYP. On this basis, through a series of optimizations in this study, a glucoside targeted molecule, which had high affinity with 4PYP and stable binding with liposome, was constructed. In summary, the use of computer-assisted screening technology could significantly accelerate the research and development efficiency of new brain-targeted molecules and provide new technical means for the design of new brain-targeted materials.

在靶向分子的指导下，以脑靶向的脂质体可以通过血脑屏障快速携带药物，从而实现药物在脑内的富集，因此，靶向分子的设计是制备高效药物的关键。脑靶向脂质体。在这项研究中，使用SYBYL-X2.1.1软件研究目标分子结构设计中每个片段结构（葡萄糖片段，脂肪链和胆固醇片段）的数量和连接方式。GROMACS用于计算分子动力学模拟，而G_MMPBSA用于计算结合自由能。结果表明，葡萄糖分子通过氢键和范德华力与4PYP相互作用。葡萄糖苷分子中的葡萄糖量和脂肪链的长度对分子与4PYP之间的相互作用具有重要影响。在此基础上，通过本研究的一系列优化，构建了与4PYP亲和力高且与脂质体稳定结合的葡萄糖苷靶向分子。综上所述，使用计算机辅助筛查技术可以显着提高新型脑靶向分子的研发效率，为新型脑靶向材料的设计提供新的技术手段。