Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China.
Shanghai Center for Bioinformation Technology & Shanghai Engineering Research Center of Pharmaceutical Translation, Shanghai Industrial Technology Institute, Shanghai 201203, China.
Acta Pharmacol Sin. 2020 Jan;41(1):138-144. doi: 10.1038/s41401-019-0228-6. Epub 2019 Jul 1.
As the number of elucidated protein structures is rapidly increasing, the growing data call for methods to efficiently exploit the structural information for biological and pharmaceutical purposes. Given the three-dimensional (3D) structure of a protein and a ligand, predicting their binding sites and affinity are a key task for computer-aided drug discovery. To address this task, a variety of docking tools have been developed. Most of them focus on docking in the preset binding sites given by users. To automatically predict binding modes without information about binding sites, we developed a user-friendly blind docking web server, named CB-Dock, which predicts binding sites of a given protein and calculates the centers and sizes with a novel curvature-based cavity detection approach, and performs docking with a popular docking program, Autodock Vina. This method was carefully optimized and achieved ~70% success rate for the top-ranking poses whose root mean square deviation (RMSD) were within 2 Å from the X-ray pose, which outperformed the state-of-the-art blind docking tools in our benchmark tests. CB-Dock offers an interactive 3D visualization of results, and is freely available at http://cao.labshare.cn/cb-dock/.
随着已阐明蛋白质结构数量的快速增加,不断增长的数据需要高效利用结构信息的方法,以用于生物和制药目的。给定蛋白质和配体的三维 (3D) 结构,预测它们的结合位点和亲和力是计算机辅助药物发现的关键任务。为了解决这个问题,已经开发了多种对接工具。其中大多数都集中在根据用户给定的预设结合位点进行对接。为了在没有结合位点信息的情况下自动预测结合模式,我们开发了一个用户友好的盲目对接网络服务器,名为 CB-Dock,它预测给定蛋白质的结合位点,并使用新颖的基于曲率的腔检测方法计算中心和大小,并使用流行的对接程序 Autodock Vina 进行对接。该方法经过仔细优化,在我们的基准测试中,其排名前几位的构象的成功率约为 70%,这些构象的均方根偏差 (RMSD) 在 2Å以内,优于最先进的盲目对接工具。CB-Dock 提供了结果的交互式 3D 可视化,并可在 http://cao.labshare.cn/cb-dock/ 上免费获取。
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