据统计，约有三分之一的药物是卤代衍生物。因此，在分子结构中引入卤素原子对创新药物研究具有重要意义。但到目前为止，还没有准确可靠的药物设计方法及软件可用来模拟预测卤代作用对化合物活性的影响，制约了药物设计方法在含卤药物的虚拟筛选、设计及优化过程中的应用研究。药物分子中的卤素与受体蛋白间作用复杂：卤素不仅可以和靶标蛋白形成性质特殊的卤键，而且可以同时形成氢键或静电作用。本申请项目将系统地研究卤素与靶标蛋白间的复杂作用机制，发展包含卤键作用的打分函数，完善卤素的可极化力场，实现包含卤键作用的高通量虚拟筛选和分子模拟，为含卤素药物的研究开发提供理论工具和新型药物先导化合物。

There are roughly one third of the marked drugs containing halogen atom substituent. Therefore, halogenation is of essential importance to drug discovery and development. However, no proper Computer-Aided-Drug-Design (CADD) method and reliable program available to date for modeling and predicting the effect of halogenation on compound bioactivity, restricting the application of CADD on the virtual screening, drug design and optimization of halogenated drugs. The interaction between halogen atoms and drug target are very complicated: not only do the halogen atoms form halogen bond with heavy atoms of target protein, but they also form hydrogen bond or electrostatic interaction separately or simultaneously. This project is designed to explore the complex interaction between halogen atoms and target protein, to develop scoring function of halogen bond, and to improve the polarizable force field of halogen atoms. The final goal of this project is to provide reliable theoretical tool and program for high throughput virtual screening and molecular modeling for discovering and designing halogenated drugs by accurately taking into account of halogen bonding.