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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.
The three-dimensional structure of DON single chain antibody was constructed and optimized by homology modeling and molecular mechanics, and the reasonable antibody model was evaluated by the combination of Procheck and verify_3D methods.The molecular docking was used to study the recognition and mutual recognition of single chain antibody and its antigen DON .The results showed that the toxin binds to the light chain of the antibody and binds to the heavy chain through the junction of the light and heavy chains and has a hydrogen bond with the residue Pro 107. The molecular dynamics simulation and MM / The binding free energy between DON and antibody is in good agreement with the experimental data, and the hydrophobic interaction of the system is the main driving force to maintain the stable structure of the complex.Kinetic simulation of hydrogen bond analysis and energy decomposition results show that the participation of residue Pro107 The formation of stable hydrogen bonds and the contribution of a strong van der Waals role is the most critical residue of the toxin-bound antibody.This study provides important clues and theoretical basis for the structural design of the toxin antibody, the research on new antibodies to toxin molecules and Development has the value of theoretical guidance.