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A comparison of various optimization algorithms of protein–ligand docking programs by fitness accuracy

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Abstract

In protein–ligand docking, an optimization algorithm is used to find the best binding pose of a ligand against a protein target. This algorithm plays a vital role in determining the docking accuracy. To evaluate the relative performance of different optimization algorithms and provide guidance for real applications, we performed a comparative study on six efficient optimization algorithms, containing two evolutionary algorithm (EA)-based optimizers (LGA, DockDE) and four particle swarm optimization (PSO)-based optimizers (SODock, varCPSO, varCPSO-ls, FIPSDock), which were implemented into the protein–ligand docking program AutoDock. We unified the objective functions by applying the same scoring function, and built a new fitness accuracy as the evaluation criterion that incorporates optimization accuracy, robustness, and efficiency. The varCPSO and varCPSO-ls algorithms show high efficiency with fast convergence speed. However, their accuracy is not optimal, as they cannot reach very low energies. SODock has the highest accuracy and robustness. In addition, SODock shows good performance in efficiency when optimizing drug-like ligands with less than ten rotatable bonds. FIPSDock shows excellent robustness and is close to SODock in accuracy and efficiency. In general, the four PSO-based algorithms show superior performance than the two EA-based algorithms, especially for highly flexible ligands. Our method can be regarded as a reference for the validation of new optimization algorithms in protein–ligand docking.

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Acknowledgments

JW thanks the National Science Foundation for support. We thank Xiakun Chu for polishing the manuscript and Erkang Wang for enlightening comments on the research. LYG, ZQY, and XLZ are supported by the National Natural Science Foundation of China (Grants 21190040, 11174105 and 91227114).

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Authors and Affiliations

  1. College of Computer Science & Technology, Jilin University, Changchun, Jilin, 130012, China

    Liyong Guo & Liang Hu

  2. State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China

    Zhiqiang Yan, Xiliang Zheng & Jin Wang

  3. Center for Molecular Medicine, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, 116024, China

    Yongliang Yang

  4. Department of Chemistry and Physics, State University of New York, Stony Brook, NY, 11794-3400, USA

    Jin Wang

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  1. Liyong Guo
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  4. Liang Hu
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  6. Jin Wang
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Correspondence to Jin Wang.

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Guo, L., Yan, Z., Zheng, X. et al. A comparison of various optimization algorithms of protein–ligand docking programs by fitness accuracy. J Mol Model 20, 2251 (2014). https://doi.org/10.1007/s00894-014-2251-3

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  • DOI: https://doi.org/10.1007/s00894-014-2251-3

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