Ansar Samdani, Sadhasivam Anupriya, Vetrivel Umashankar
1Centre for Bioinformatics, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Vision Research Foundation, SankaraNethralaya, Chennai - 600 006, Tamil Nadu, India.
2School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, India.
Bioinformation. 2019 Apr 15;15(4):295-298. doi: 10.6026/97320630015295. eCollection 2019.
Functional characterisation of proteins often depends on specific interactions with other molecules. In the drug discovery scenario, the ability of a protein to bind with drug-like molecule with a high affinity is referred as druggability. Deciphering such druggable binding pockets on proteins plays an important role in structure-based drug designing studies. Moreover, availability of plethora of structural data poses a need automated pipelines which can efficiently integrate robust algorithms towards large-scale pocket identification and comparison. These pipelines have direct applicability on off-target analysis, drug repurposing and structural prioritization of drug targets in pathogenic microbes. However, currently there is a paucity of such efficient pipelines. Hence, by this study a highly optimized shell script based pipeline (PocketPipe) has been developed with seamless integration of robust algorithms namely, P2Rank (predicts binding sites based on machine learning) and PocketMatch-v2.1 (compares binding pockets by residue-based method), for pocketome generation and comparison, respectively. The process of input workflow and various steps carried out by PocketPipe and the output results are well documented in the operating manual. On execution, the pipeline features seamless operability, high scalability, dynamic file handling and results parsing. PocketPipe is distributed freely under GNU GPL license and can be downloaded at https://github.com/inpacdb/PocketPipe.
蛋白质的功能表征通常取决于与其他分子的特定相互作用。在药物发现的情境中,蛋白质与类药物分子高亲和力结合的能力被称为可成药性。解析蛋白质上这种可成药的结合口袋在基于结构的药物设计研究中起着重要作用。此外,大量结构数据的可用性使得需要自动化流程,这些流程能够有效地整合强大的算法以进行大规模口袋识别和比较。这些流程在脱靶分析、药物再利用以及病原微生物中药物靶点的结构优先级确定方面具有直接适用性。然而,目前缺乏这样高效的流程。因此,通过本研究,开发了一种基于高度优化的 shell 脚本的流程(PocketPipe),它无缝集成了强大的算法,即 P2Rank(基于机器学习预测结合位点)和 PocketMatch-v2.1(通过基于残基的方法比较结合口袋),分别用于口袋组的生成和比较。输入工作流程以及 PocketPipe 执行的各个步骤和输出结果在操作手册中有详细记录。执行时,该流程具有无缝可操作性、高可扩展性、动态文件处理和结果解析功能。PocketPipe 根据 GNU GPL 许可免费分发,可在 https://github.com/inpacdb/PocketPipe 下载。