自旋交叉在含过渡金属的酶催化反应中广泛存在，是两态反应体系的重要特征，给这些体系的力场开发提出了新的挑战。主要表现在两个方面，一是需要力场能够同时描述多个自旋态，二是在自旋交叉区域，需要根据力场直接计算跃迁几率。目前，同时满足这两个要求的力场鲜有报导。本项目拟开发多自旋态可变电荷力场，以血红素模型体系为代表实现多自旋态的分子动力学模拟。首先，为了使力场能够描述多自旋态，拟从数据驱动的思想出发，采用从头算动力学方法采样构建结构数据集，通过聚类、网络等方法对数据集和轨迹进行分析获得代表结构集，采用代表结构加权的方法实时预测各自旋态电荷，开发多自旋态可变电荷力场。其次，在分子动力学中引入Zhu-Nakamura非绝热跃迁算法处理自旋交叉过程，这一算法只需要力场提供能量和梯度作为输入，可实现血红素模型体系多自旋态的分子动力学模拟。本项目研究思路具有很好的可拓展性，可为其它类似力场的研究提供借鉴。

Spin crossover is a major feature of two states reaction mechanism, which exists broadly in reactions of transition metal enzymes. At the same time, spin crossover makes a new challenge to force field development of these systems. Two questions should be addressed in the development of the force field for these systems. Firstly, the force field should be able to describe multi spin states simultaneously. Secondly, new methods should be adopted to calculate the switching probability in spin crossover region. Currently, force field that fit both of these features is still rarely reported. In this project, we proposed to development of multi spin states updateable charge force filed for heme models and apply the force field to multi spin states molecular dynamic simulation. At the first place, we use data driving model to build multi spin states updateable charge force filed. The trajectory of on-the-fly molecular dynamic simulation would be clustered into several classes and each class is represented by a structure. The multi spin states parameters of interested structures would, then, be calculated by a weighted average method. Meanwhile, the modified Zhu-Nakamura method is introduced into molecular dynamic simulation for calculating the switching probability in spin crossover region. This algorithm requires only energy and grad as input, both of which are outputs from force field. The multi spin states molecular dynamic simulations will be performed in the project and with heme model system as test. This strategy is also helpful to the developments of force fields for other transition metal enzymes.