Abstract: OBJECTIVE: Virtual screening of potential small molecule inhibitors of acetylcholinesterase (AChE) in Cistanche tubulosa compound preparations,while providing reference for the discovery of new AChE inhibitors. METHODS: A virtual screening database of Cistanche tubulosa, ginseng and astragalus was established based on the traditional Chinese medicine system pharmacology technology platform (TCMSP) and literature retrieval. The Glide molecule was docked by Rosetta software,and a wide range of Box was formed by using the amino acid residues around the active site of AChE receptor. Different types of components were used as probes to scan, and the lattice energy was calculated for energy ranking. After that, conformation of the ligand in the range of Box was searched,and the results were scored according to the different conformation, direction,position and energy of the ligand. Finally,the SPR technology was used to verify the binding force of the main active components and AChE protein. RESULTS: The binding mode and binding energy of AChE protein to the typical lead compounds selected from each system were good. In the molecular docking system of all compounds, Cistanche tubulosa energy scored between -9.397~-0.858 kcal/mol, ginseng energy score between -9.929~-0.211 kcal/mol and astragalus energy scored between -9.408~-1.555 kcal/mol. The docking energies of all compounds were less than -7.0 kcal/mol. The results of SPR affinity test showed that quercetin, kaempferol and genistein all showed good binding ability to AChE protein. CONCLUSION: The presence of AChE inhibitors in Cistanche tubulosa compound preparation was screened based on molecular docking technique, and the good affinity between AChE protein and active components was verified by SPR technique.

Key words: acetylcholinesterase, Cistanche tubulosa compound preparation, molecular docking virtual screening, surface plasmon resonance