复杂生物体系介观尺度动态结构与相互作用的理论计算化学研究

分子动力学模拟是连接冷冻电镜等结构解析技术得到的静态结构与近生理环境下生物分子行使功能的动态结构及相互作用的最佳研究手段。现有理论化学研究都是针对单个生物分子及其复合物在纳米和微秒时空尺度下进行动力学模拟与微观机理解析，与实验所观测到的介观尺度（微米和毫秒）有非常大差距，亟需提出和发展新的理论模型及模拟方法。本项目基于我们前期提出和发展的蛋白质量子分块计算方法、全原子可极化和高精度粗粒化细胞膜模型及其模拟方法，建立量子精度膜生物体系及其高效模拟方法，发展自定义粗粒度的通用粗粒化方法，构建复杂生物体系的新型有限元模型及其模拟方法，实现细粒度模型计算与深度学习技术相结合的高精度粗粒度模型计算方案，并通过不同尺度动力学模拟之间有机融合增强复杂生物体系细粒度模型的构象采样效率，最终形成一套高精度介观时空尺度生物体系的高效理论模拟新方法，并针对神经兴奋传递的膜动作电位产生和传导分子机制开展应用研究。

Molecular dynamics simulation is the best research method for static structure obtained by structural analysis techniques such as cryo-electron microscopy and the function of biomolecules dynamic structure in the near physiological environment and interaction. Existing theoretical chemistry studies are aimed at kinetic simulation and microscopic mechanism analysis of single biomolecules and their complexes at nanometer and microsecond spatiotemporal scales, which are very different from the mesoscales (microns and milliseconds) observed in the experiments. There is an urgent need to propose and develop new theoretical models and simulation methods. This project is based on the protein quantum block calculation method, the all-atom polarizable and high-precision coarse-grained cell membrane model and its simulation method , the quantum precision membrane biological system and its efficient simulation method proposed and developed by us in the early stage. A general coarse-grained method of particle size, a new finite element model for complex biological systems and its simulation method, a high-precision coarse-grained model calculation scheme combining fine-grained model calculation and deep learning technology, and simulated by different scale dynamics Inter-organic fusion enhances the conformation sampling efficiency of the fine-grained model of complex biological systems, and finally a set of high-efficiency theoretical simulation methods for high-precision mesoscopic space-time biological systems was developed, and applied research on membrane action potential generation and conduction molecular mechanisms of neural excitation.