多尺度模拟方法研究铀镎与运铁蛋白的相互作用

针对铀、镎对环境与健康的影响，拟采用基于量子化学和分子力场的QM/MM方法，研究铀、镎与运铁蛋白的相互作用，对铀、镎在蛋白质环境中的配位相互作用模式进行表征，探索在铀镎与蛋白结合、复合状态和释放过程中起关键作用的氨基酸残基。本项目对阐明铀、镎与生物大分子的作用机制，揭示影响铀、镎在生物体内迁移的因素、推广多尺度模拟方法在锕系化学研究中的应用有重要意义。通过研究将促进多尺度模拟方法在锕系化学研究中的应用，提出改变运铁蛋白与铀镎相互作用的蛋白质设计方案，为减低铀镎对环境与健康的影响提供理论支持。

This project targets on the influence of uranium(U) and neptunium (Np) on environment and human health, and by using combined quantum mechanics (QM) and molecular mechanics (MM) methodology (QM/MM), the interaction between U, Np and transferrin (Tf) will be investigated to characterize the coordination chemistry of U and Np in the protein environment and to pin down the key amino acid residues that are crucial to the binding of U and Np to Tf, including their uptake, complexation, and release. Expectively this project will contribute to elucidate the binding mechanism of U and Np to Tf, to unravel the factors that influence their transport in bloodstream and to advance the application of QM/MM methodology in computational actinide chemistry. The outcome of the project may guide the rational design of proteins towards the binding of actinides.