毒素don 单链抗体的同源建模及与don 结合的分子模拟研究 .pdf

2011 年第 69 卷 化 学 学 报 Vol. 69, 2011 第 23 期, 2882～2888 ACTA CHIMICA SINICA No. 23, 2882～2888 ·研究论文· 毒素 DON 单链抗体的同源建模及与 DON 结合的分子模拟研究 郑 蓉 吕 暾* (福州大学生物科学与工程学院 福州 350108) 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. 关键词 DON; 抗体设计; 结合自由能; 同源建模; 分子对接 Homology Modeling of Anti-DON Scfv Antibody and Molecular Simulation Study between Scfv and Its Antigen DON Zheng, Rong Lü, Tun* (Institute of Biological Science and Engineering, Fuzhou University, Fuzhou 350108) Abstract The three dimensional structure of anti-DON Scfv antibody was modeled and refined using ho- mology modeling and molecular mechanics methods. Procheck and verify_3D methods were used to con- firm 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