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The B-factor index for the binding site (BFIbs) to prioritize crystal protein structures for docking

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Abstract

In cheminformatics, protein-ligand docking is a powerful tool applied for virtual screening, pose prediction, and binding affinity estimation. However, docking results depend on the quality of the crystal protein structures. Although several crystallographic indices can assist the selection of proteins, these are often misused by non-experts or have little applicability. Hereby, we propose the B-factor index for the binding site (BFIbs), which indicates the atomic fluctuations of the atoms in the binding site in comparison with atoms in the protein. Using an automated docking workflow, we performed docking experiments on 26,019 protein-ligand complexes. The docking performances were analyzed based on five crystallographic quality indices, i.e., BFIbs, DPI (the diffraction–component precision index), DPIbs (DPI of the binding site atoms), RRfree (R–Rfree), and the resolution of the X-ray crystal structure. Only BFIbs was found to significantly correlate with the root–mean–square deviation (RMSD) computed between the ligand poses in the crystal structures and the predicted docking poses. The majority of the best docking results (RMSD < 2 Å) were indicated by BFIbs < 1. We conclude that BFIbs, as a simple and interpretable parameter that complements other indices, can help to effectively prioritize protein structures for structure-based cheminformatics.

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Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

The code used for data generation and/or analysis within the current study is available from the corresponding author on reasonable request.

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Acknowledgements

The authors wish to thank Dr. Ramona Curpan for constructive comments and suggestions regarding the manuscript.

Funding

This work was supported by project number 1.1.4/2019/2020, of “Coriolan Drăgulescu” Institute of Chemistry, Timișoara, Romanian Academy, Romania.

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Authors and Affiliations

  1. Department of Computational Chemistry, “Coriolan Dragulescu” Institute of Chemistry, 24 Mihai Viteazu Av, 300223, Timişoara, Timiş, Romania

    Liliana Halip, Sorin Avram & Cristian Neanu

Authors
  1. Liliana Halip
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  2. Sorin Avram
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  3. Cristian Neanu
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Contributions

Cristian Neanu and Sorin Avram contributed to the conception and design of this study. Liliana Halip and Cristian Neanu performed the molecular docking experiment and Sorin Avram developed the decision tree. All authors contributed to the manuscript writing and approved the final manuscript.

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Correspondence to Cristian Neanu.

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Halip, L., Avram, S. & Neanu, C. The B-factor index for the binding site (BFIbs) to prioritize crystal protein structures for docking. Struct Chem 32, 1693–1699 (2021). https://doi.org/10.1007/s11224-021-01751-9

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  • DOI: https://doi.org/10.1007/s11224-021-01751-9

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