摘要
目的发现新的CXCR4抑制剂,进一步对筛选出的抑制剂与CXCR4的分子结合模型进行分析.方法以CXCR4为靶点,应用基于AutoDock Vina的新的虚拟筛选工具PyRx对ZINC数据库中的化合物进行虚拟筛选.CXCR4晶体结构(PDB ID:3ODU)从PDB下载,通过AutoDockTools对结构进行处理.化合物的三维结构从ZINC数据库下载,通过虚拟筛选工具PyRx导入,转换成pdbqt格式.PyRx运行AutoDock Vina以后,筛选以后的化合物构象导入AutoDockTools进行分析,数据处理用PyMOL完成.结果经过高通量虚拟筛选,从ZINC数据库中大约2万个化合物中得到1 000个类药小分子化合物数据库,再从中进一步筛选靶向CXCR4的抑制剂.经过对建立的化合物数据库的3轮筛选,发现了5个高活性的CXCR4抑制剂.结论应用基于AutoDock Vina的新的虚拟筛选工具PyRx,以CXCR4为靶点,对ZINC数据库的2万个化合物进行虚拟筛选,发现5个新的CXCR4抑制剂.
Objective The aim of this study was to discover new CXCR4 inhibitors and build 3D interaction model between these inhibitors and CXCR4,through virtual screening the 20000 compounds in ZINC database by using new virtual screening tools of PyRx to run AutoDock Vina. Methods The study focused on the target of CXCR4,through virtual screening program of AutoDock Vina to virtual screen the compounds in ZINC database.New virtual screening tools of PyRx was used to run AutoDock Vina. The CXCR4 crystal structure（PDB ID： 3ODU）was downloaded from PDB and modified with AutoDock Tools. Compounds＇ structures were downloaded from ZINC database and imported with PyRx, then processed into format of pdbqt. The post-screening compounds were imported into AutoDockTools,and the data were outputted with PyMOL. Results There were 1 000 small molecular compounds for high-throughput screening from about 20000 compounds in the library. After screening for three times,we found five highly active CXCR4 inhibitors from the 1000 small molecular compounds. Conclusion By using the tools of PyRx to run AutoDock Vina, we found five new compounds of CXCR4 inhibitors from ZINC database.
出处
《昆明医科大学学报》
CAS
2014年第9期44-47,共4页
Journal of Kunming Medical University
基金
贵州省科技厅联合基金资助项目(黔科合J字LKZ[2013]21号)
遵义医学院博士启动基金资助项目(谷万港博士主持)
遵义医学院大学生创新实验计划项目(院发[2013]6502)
