中文摘要：

通过同源模建及分子力学构建并优化了呕吐毒素DON单链抗体的三维结构,结合Procheck和verify_3D方法评估得到合理的抗体模型.利用分子对接方法研究了单链抗体与其抗原DON的识别及相互作用.结果表明,毒素结合到抗体轻链上,通过轻重链的交界区残基与重链结合,与残基Pro107之间存在氢键作用.采用分子动力学模拟和MM/GBSA方法计算了毒素DON与抗体之间的结合自由能,计算结果与实验值相吻合,体系疏水相互作用是维持复合物稳定结构的主要驱动力.动力学模拟氢键分析和能量分解结果共同表明,残基Pro107参与稳定氢键的形成并贡献很强的范德华作用,是毒素结合抗体最关键的残基.本研究为该毒素抗体的结构设计提供了重要的线索和理论依据,对毒素类分子新型抗体的研究和开发具有理论指导价值.

英文摘要：

The three dimensional structure of anti-DON Scfv antibody was modeled and refined using homology modeling and molecular mechanics methods.Procheck and verify_3D methods were used to confirm the model＇s reliability.The recognition and interaction between voitoxin DON and its Scfv antibody were studied via molecular docking method.The result indicated that DON located at the active site of chain VL,binding to VH by several residues in their critical region,and formed a hydrogen bond with residue Pro107.Molecular dynamics simulation and MM/GBSA methods were used to calculate the binding free energy between DON and its Scfv.The calculated binding free energy agreed with experimental index.It was also indicated that the formation of this complex was mainly driven by the hydrophobic interaction.Hydrogen bond analysis and energy decomposition showed that Pro107 was the most important residue which contributed a stable hydrogen bond and strong van der Waals＇ interaction.This research provides some important clues for structure design of anti-DON Scfv antibody,and useful theoretical instruction for the study and development of new types Scfv of toxin-like small molecules.