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SAMPL6 host–guest binding affinities and binding poses from spherical-coordinates-biased simulations

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Abstract

Host–guest binding is a challenging problem in computer simulation. The prediction of binding affinities between hosts and guests is an important part of the statistical assessment of the modeling of proteins and ligands (SAMPL) challenges. In this work, the volume-based variant of well-tempered metadynamics is employed to calculate the binding affinities of the host–guest systems in the SAMPL6 challenge. By biasing the spherical coordinates describing the relative position of the host and the guest, the initial-configuration-induced bias vanishes and all possible binding poses are explored. The agreement between the predictions and the experimental results and the observation of new binding poses indicate that the volume-based technique serves as a nice candidate for the calculation of binding free energies and the search of the binding poses.

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Acknowledgements

This work was supported China Scholarship Council. Computer access to the CLAIX cluster of RWTH Aachen University and clusters of Forschungszentrum Juelich is gratefully acknowledged. We are grateful for many valuable and insightful comments from the anonymous reviewers.

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Authors and Affiliations

  1. Computational Biomedicine (IAS-5/INM-9), Forschungszentrum Jülich, 52425, Jülich, Germany

    Zhaoxi Sun

  2. State Key Laboratory of Precision Spectroscopy, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China

    Zhaoxi Sun

  3. School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China

    Qiaole He

  4. Physics, Engineering, Earth, Environment, Mechanics (PhITEM), University Grenoble Alpes, 38000, Grenoble, France

    Xiao Li

  5. CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China

    Zhengdan Zhu

  6. University of Chinese Academy of Sciences, Beijing, 100049, China

    Zhengdan Zhu

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Sun, Z., He, Q., Li, X. et al. SAMPL6 host–guest binding affinities and binding poses from spherical-coordinates-biased simulations. J Comput Aided Mol Des 34, 589–600 (2020). https://doi.org/10.1007/s10822-020-00294-1

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