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(How to) Profit from Molecular Dynamics-based Ensemble Docking

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Application of Computational Techniques in Pharmacy and Medicine

Part of the book series: Challenges and Advances in Computational Chemistry and Physics ((COCH,volume 17))

Abstract

Computational techniques have provided the field of drug discovery with enormous advances over the last decades. The development of methods covering dynamical aspects in protein–ligand binding is currently leading computer-aided drug design to new levels of complexity as well as accuracy. In this book chapter we focus on molecular docking to structural ensembles generated by molecular dynamics (MD) simulations. Does the incorporation of multiple receptor conformations allow pushing the borders for molecular docking or does it just lead to an artificial increase in false positive hit rates due to a broader conformational space of the receptor? We aim to identify guidelines for the best practice of molecular dynamics simulation-based ensemble docking from recent studies in the literature. Hence, we split the computational workflow for MD-based ensemble docking into the respective steps starting from protein structure and compound database to in silico hit lists. Thereby, we focus on the identification of successful strategies for virtual screening.

Susanne von Grafenstein and Julian E. Fuchs authors contributed equally.

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Acknowledgments

Presented work was supported by funding of the Austrian Science Fund FWF: project “Targeting Influenza Neuraminidase” (P23051). Julian E. Fuchs is a recipient of a DOC-fellowship of the Austrian Academy of Sciences at the Institute of General, Inorganic and Theoretical Chemistry at University of Innsbruck.

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  1. Institute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, 6020, Innsbruck, Austria

    Susanne von Grafenstein, Julian E. Fuchs & Klaus R. Liedl

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  1. Susanne von Grafenstein
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  2. Julian E. Fuchs
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  3. Klaus R. Liedl
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Correspondence to Klaus R. Liedl .

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  1. Department of Molecular Biophysics, Laboratory of Computational Structural Biology, Kiev, Ukraine

    Leonid Gorb

  2. Department of Molecular Structure and Chemoinformatics, A.V. Bogatsky Physical-Chemical Institute, National Academy of Sciences of Ukraine, Odessa, Ukraine

    Victor Kuz'min

  3. Department of Chemical Biology and Medicinal Chemistry, University of North Carolina, Laboratory for Molecular Modeling, Chapel Hill, North Carolina, USA

    Eugene Muratov

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von Grafenstein, S., Fuchs, J., Liedl, K. (2014). (How to) Profit from Molecular Dynamics-based Ensemble Docking. In: Gorb, L., Kuz'min, V., Muratov, E. (eds) Application of Computational Techniques in Pharmacy and Medicine. Challenges and Advances in Computational Chemistry and Physics, vol 17. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9257-8_15

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