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目的:通过计算机辅助分子模拟,解析抗乙酰胆碱酯酶(AChE)单克隆抗体3F3抑酶的分子基础。方法:用柔性连接肽(Gly_4Ser)_3连接V_H及V_L设计3F3单链抗体(Sc3F3)。将重组的Sc3F3的氨基酸序列进行计算机辅助分子模建,并与抗原分子AChE对接,模拟抗原抗体反应的三维模式。结果:模拟的Sc3F3结构具有经典抗体的共性特征,抗体的重链和轻链可变区都含有两个β片层和片层连接区。单链抗体与AChE相互作用对接图显示形成了稳定的结构。范德华力起着重要的作用,提示Sc3F3与AChE通过疏水作用形成复合物。结论:从Sc3F3与AChE形成复合物的空间结构看出Sc3F3结合在胆碱酯酶活性中心狭缝的入口处,对底物进入活性中心起到阻碍作用。
OBJECTIVE: To elucidate the molecular basis of anti-acetylcholinesterase (AChE) monoclonal antibody 3F3 by computer-aided molecular modeling. Methods: 3F3 single chain antibody (Sc3F3) was designed by connecting V_H and V_L with flexible linker peptide (Gly_4Ser) _3. The recombinant Sc3F3 amino acid sequence of computer-assisted molecular modeling, docking with the antigen molecule AChE, mimicking the three-dimensional pattern of antigen-antibody reaction. RESULTS: The simulated Sc3F3 structure shared the common features of classical antibodies. The heavy and light chain variable regions of the antibody contained two β-sheet and lamellar junctions. Single chain antibodies interact with AChE Docking plots show the formation of a stable structure. Van der Waals forces play an important role, suggesting that Sc3F3 and AChE through hydrophobic interaction to form a complex. Conclusion: From the spatial structure of the complex formed by Sc3F3 and AChE, it is found that Sc3F3 binds to the entrance of cholinesterase active center slits and hinders the substrate from entering the active center.