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Molecular Docking Studies to Explore Potential Binding Pockets and Inhibitors for Chikungunya Virus Envelope Glycoproteins

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Abstract

The chikungunya virus (CHIKV) envelope glycoproteins are considered important potential targets for anti-CHIKV drug discovery due to their crucial roles in virus attachment and virus entry. In this study, using two available crystal structures of the immature and mature forms of envelope glycoproteins, virtual screenings based on blind dockings and focused dockings were carried out to identify potential binding pockets and hit compounds for the virus. The chemical library database of compounds, NCI Diversity Set II, was used in these docking studies. In addition to reproducing previously reported examples, new binding pockets were identified, e.g., Pocket 2 in the 3N40, and Pocket 2 and Pocket 3 in the 3N42. Convergences in conformational sampling in docking using AutoDock Vina were evaluated. An analysis of docking results was carried out to understand interactions of the envelope glycoproteins complexes. Some key residues for interactions, for example Gly91 and His230, are identified as possessing important roles in the fusion process.

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Acknowledgements

PTVN was supported by a UOW-Vietnamese Government Scholarship (VIED-MOET). H.Y. is the recipient of an Australian Research Council Future Fellowship (Project number FT110100034). This research was undertaken with the assistance of resources provided at the University of Wollongong High Performance Computing Cluster.

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Correspondence to Haibo Yu or Paul A. Keller.

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Nguyen, P.T.V., Yu, H. & Keller, P.A. Molecular Docking Studies to Explore Potential Binding Pockets and Inhibitors for Chikungunya Virus Envelope Glycoproteins. Interdiscip Sci Comput Life Sci 10, 515–524 (2018). https://doi.org/10.1007/s12539-016-0209-0

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  • DOI: https://doi.org/10.1007/s12539-016-0209-0

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