Centre for Bioinformatics, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Vision Research Foundation, Sankara Nethralaya, Chennai, India.
School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, India.
Chem Biol Drug Des. 2020 Oct;96(4):1162-1175. doi: 10.1111/cbdd.13705. Epub 2020 Jun 20.
Kinases are key targets for many of the pathological conditions. Inverse screening of ligands serves as an essential mode to identify potential kinase targets in modern drug discovery research. Hence, we intend to develop KinomeRun, a robust pipeline for inverse screening and kinome tree visualization through the seamless integration of kinome structures, docking and kinome-drug interaction fingerprint analysis. In this pipeline, the hurdle of residue numbering in kinome is also resolved by creating a common index file with the conserved kinase pocket residues for comparative interaction analysis. KinomeRun can be used to screen the ligands of interest docked against multiple kinase structures in parallel around the kinase binding site and also to filter out the targets with unique interaction patterns. This automation is essential for prioritization of kinase targets that show specificity for a given drug and will also serve as a crucial tool kit for holistic approaches in kinase drug discovery. KinomeRun is developed using python and bash programming language and is distributed freely under the GNU GPL licence-3.0 and can be downloaded at https://github.com/inpacdb/KinomeRun. The tutorial videos for installation, target screening and customized filtration are available at https://www.youtube.com/playlist?list=PLuIaEFtMVgQ7v__WigQH9ilGVxrfI1LKs and also be downloaded for offline viewing from the github link.
激酶是许多病理状况的关键靶点。配体的反向筛选是现代药物发现研究中识别潜在激酶靶点的重要模式。因此，我们旨在开发 KinomeRun，这是一个强大的反向筛选和激酶树可视化管道，通过无缝集成激酶结构、对接和激酶-药物相互作用指纹分析来实现。在这个管道中，通过为保守的激酶口袋残基创建一个通用索引文件，解决了激酶中残基数目的障碍，以便进行比较相互作用分析。KinomeRun 可用于同时筛选针对激酶结合位点的多个激酶结构的感兴趣的配体，也可用于筛选具有独特相互作用模式的靶标。这种自动化对于优先考虑对特定药物具有特异性的激酶靶标至关重要，也将成为激酶药物发现整体方法的重要工具包。KinomeRun 使用 Python 和 bash 编程语言开发，并根据 GNU GPL 许可证-3.0 免费分发，可以在 https://github.com/inpacdb/KinomeRun 上下载。安装、目标筛选和定制过滤的教程视频可在 https://www.youtube.com/playlist?list=PLuIaEFtMVgQ7v__WigQH9ilGVxrfI1LKs 上观看，也可以从 github 链接下载以供离线观看。
