基于蛋白质科学（上海）设施5线6站高通量线站BL17B的自动化药物筛选系统的开发

BL17B, located in Shanghai Synchrotron Radiation Facility (SSRF), is one of the most important protein crystallographic beamlines that constructed by National Protein Sciences (Shanghai) Facility (NPSF). BL17B using bending magnet(BM) as x-ray source and MD2+MX300+Rigaku Actor in Endstation, is designed as a beamline that has the ability of automatic data collection and high throughput structure solution for normal protein crystals. Structure-based drug design is a hot spot in drug research area all over the world. Because of the high ability for illustrating the interaction mechanism of protein-protein and protein-ligand in atomic level, protein crystallography, as one of the most important parts of structure-based drug design, is receiving more and more attention. Rather than structure biology, which aims at solving a novel protein structure or a novel protein-protein complex to explicate a task in biology, protein crystallography in structure-based drug design focuses on the interaction between protein and ligand, while the structure of protein may probably be solved before. In order to improve the efficiency of BL17B, an automatic drug screening system is to be developed and integrated in the user programs of BL17B. Besides of automatic data collection, the system will also contain automatic diffraction data process (including data index, space group determination and data integration), automatic protein structure determination (probably using the method of molecular replacement), and automatic ligand recognition.

基于X射线晶体学的蛋白质与配体相互作用研究是生物医药研发中确定药物先导化合物十分的重要手段。2013年底建成的蛋白质（上海）设施5线6站中的3条大分子晶体学线站在国内生物医药研发中将发挥重要的作用。本自动化先导药物筛选系统，将以5线6站中的大分子晶体学线站BL17B为依托，参考当前生物大分子晶体学同步辐射线站最新的实验技术以及大分子X射线晶体结构解析的最新方法来进行开发。本系统包括：晶体衍射数据的自动收集，自动处理；蛋白质晶体结构的自动解析和配体位置的自动搜索。整个系统将封装在一个用户友好的界面下，使得用户可以很容易的使用，并迅速得到正确的实验结果。本系统的成功研发，在大大提高同步辐射线站的使用效率的同时，也降低了药物研发人员在数据收集和结构解析方面的工作量，使得研发人员可以有更多的时间和精力投入到药物研发其他阶段的工作中。