College of Information Engineering, Zhejiang University of Technology, Hangzhou 310023, China.
School of Computer Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
Bioinformatics. 2022 Jan 3;38(2):556-558. doi: 10.1093/bioinformatics/btab667.
Accurately identifying protein-ATP binding poses is significantly valuable for both basic structure biology and drug discovery. Although many docking methods have been designed, most of them require a user-defined binding site and are difficult to achieve a high-quality protein-ATP docking result. It is critical to develop a protein-ATP-specific blind docking method without user-defined binding sites.
Here, we present ATPdock, a template-based method for docking ATP into protein. For each query protein, if no pocket site is given, ATPdock first identifies its most potential pocket using ATPbind, an ATP-binding site predictor; then, the template pocket, which is most similar to the given or identified pocket, is searched from the database of pocket-ligand structures using APoc, a pocket structural alignment tool; thirdly, the rough docking pose of ATP (rdATP) is generated using LS-align, a ligand structural alignment tool, to align the initial ATP pose to the template ligand corresponding to template pocket; finally, the Metropolis Monte Carlo simulation is used to fine-tune the rdATP under the guidance of AutoDock Vina energy function. Benchmark tests show that ATPdock significantly outperforms other state-of-the-art methods in docking accuracy.
https://jun-csbio.github.io/atpdock/.
Supplementary data are available at Bioinformatics online.
准确识别蛋白质与 ATP 的结合构象对于基础结构生物学和药物发现都具有重要意义。尽管已经设计了许多对接方法，但它们大多数都需要用户定义的结合位点，并且难以实现高质量的蛋白质-ATP 对接结果。因此，开发一种无需用户定义结合位点的蛋白质-ATP 特异性盲目对接方法至关重要。
在这里，我们提出了 ATPdock，这是一种用于将 ATP 对接入蛋白质的基于模板的方法。对于每个查询蛋白质，如果没有口袋位点，则 ATPdock 首先使用 ATP-binding site predictor ATPbind 识别其最可能的口袋；然后，使用 APoc，一种口袋结构比对工具，从口袋-配体结构数据库中搜索与给定或识别的口袋最相似的模板口袋；第三，使用 LS-align，一种配体结构比对工具，生成 ATP 的大致对接构象（rdATP），以将初始 ATP 构象与模板口袋对应的模板配体对齐；最后，使用 Metropolis Monte Carlo 模拟在 AutoDock Vina 能量函数的指导下微调 rdATP。基准测试表明，ATPdock 在对接精度方面明显优于其他最先进的方法。
https://jun-csbio.github.io/atpdock/。
补充数据可在“Bioinformatics”在线获取。
