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HBGA binding modes and selectivity in noroviruses upon mutation: a docking and molecular dynamics study

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Abstract

Norovirus, also called winter vomiting bug, is the most common cause for gastroenteritis and severe childhood diarrhea disease. High mutation rates cause drug resistance and thus complicate the development of an effective therapeutics against virus infection. The virus protein enters the host cell via the interaction with histo-blood group antigens (HBGAs), formed by oligosaccharides. To date, the crystal structures of numerous complexes of virus proteins with different antigens have been reported. The HBGAs bind to the two distinct regions of the virus proteins. Herein, the affinity of different variants of virus protein to some common glycans has been computationally analyzed. Molecular docking studies as combination of docking scores and rmsd values revealed that the binding region 1 is more attractive for the ligands in variants of categories 1–5, but selectivity is drastically shifted to region 2 due to in category 6. In addition, molecular dynamics simulations were unraveled when the region 1 is hindered (in category 6); the blocking loop has less fluctuation than that of unblocked in other categories.

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Acknowledgments

The numerical calculations reported in this paper were partially performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources). AK acknowledges the Schrodinger, LLC, for providing the evaluation copy of the software.

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  1. Department of Chemistry, Gebze Technical University, 41400, Gebze, Kocaeli, Turkey

    Abdulkadir Kocak

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Kocak, A. HBGA binding modes and selectivity in noroviruses upon mutation: a docking and molecular dynamics study. J Mol Model 25, 369 (2019). https://doi.org/10.1007/s00894-019-4261-7

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