Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul 5;50(W1):W159-W164.
doi: 10.1093/nar/gkac394.

CB-Dock2: improved protein-ligand blind docking by integrating cavity detection, docking and homologous template fitting

Yang Liu  1 , Xiaocong Yang  1 , Jianhong Gan  1 , Shuang Chen  2 , Zhi-Xiong Xiao  1 , Yang Cao  1   3
Affiliations

CB-Dock2: improved protein-ligand blind docking by integrating cavity detection, docking and homologous template fitting

Yang Liu et al. Nucleic Acids Res. .

Abstract

Protein-ligand blind docking is a powerful method for exploring the binding sites of receptors and the corresponding binding poses of ligands. It has seen wide applications in pharmaceutical and biological researches. Previously, we proposed a blind docking server, CB-Dock, which has been under heavy use (over 200 submissions per day) by researchers worldwide since 2019. Here, we substantially improved the docking method by combining CB-Dock with our template-based docking engine to enhance the accuracy in binding site identification and binding pose prediction. In the benchmark tests, it yielded the success rate of ∼85% for binding pose prediction (RMSD < 2.0 Å), which outperformed original CB-Dock and most popular blind docking tools. This updated docking server, named CB-Dock2, reconfigured the input and output web interfaces, together with a highly automatic docking pipeline, making it a particularly efficient and easy-to-use tool for the bioinformatics and cheminformatics communities. The web server is freely available at https://cadd.labshare.cn/cb-dock2/.

PubMed Disclaimer

Figures

Graphical Abstract
Graphical Abstract
CB-Dock2 integrates the structure-based and template-based blind docking algorithms.
Figure 1.
Figure 1.
The overall pipeline of CB-Dock2. It is constructed by modules of data input, data processing, cavity detection and docking, and visualization and analysis.
Figure 2.
Figure 2.
The overall performance of CB-Dock2 on Astex Diverse Set. (A) The success rates of the top-ranking binding modes achieved by CB-Dock, FitDock and CB-Dock2 respectively. (B) The success rates of the top-ranking binding modes achieved by MTiAutoDock, SwissDock, COACH-D and CB-Dock2, respectively. COACH-D1 and COACH-D2 refers to that the best pose generated by COACH-D is selected based on c-score and the docking score of AutoDock Vina, respectively.
Figure 3.
Figure 3.
Output interfaces of cavity detection. (A) The cavities detected by analyzing the concave regions on the solvent accessible surface of the query protein. (B) The docking results after clicking the button of ‘BlindDock’. (C) The cavities detected based on homologus templates. (D) The docking results after clicking the button of ‘Template-based Docking’.
Figure 4.
Figure 4.
The input and output interfaces of blind docking. (A) The panel for submission of query protein. (B) The panel for submission of query ligand. (C) The job list and status of the submissions. (D) The interactive visualization and meta-analysis for the blind docking results. Users can select and highlight the docking pose for each cavity.
See this image and copyright information in PMC

References

    1. Salentin S., Schreiber S., Haupt V.J., Adasme M.F., Schroeder M.. PLIP: fully automated protein–ligand interaction profiler. Nucleic Acids Res. 2015; 43:W443–W447. - PMC - PubMed
    1. Jacob L., Vert J.P.. Protein-ligand interaction prediction: an improved chemogenomics approach. Bioinformatics. 2008; 24:2149–2156. - PMC - PubMed
    1. Hassan N.M., Alhossary A.A., Mu Y., Kwoh C.-K.. Protein-ligand blind docking using QuickVina-W with inter-process spatio-temporal integration. Sci. Rep. 2017; 7:15451. - PMC - PubMed
    1. Hetényi C., van der Spoel D.. Efficient docking of peptides to proteins without prior knowledge of the binding site. Protein Sci. 2009; 11:1729–1737. - PMC - PubMed
    1. Tunyasuvunakool K., Adler J., Wu Z., Green T., Zielinski M., Žídek A., Bridgland A., Cowie A., Meyer C., Laydon A.et al. .. Highly accurate protein structure prediction for the human proteome. Nature. 2021; 596:590–596. - PMC - PubMed

Publication types