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Molecular modeling of methyl-α-Neu5Ac analogues docked against cholera toxin - a molecular dynamics study

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Abstract

Molecular modeling of synthetic methyl-α-Neu5Ac analogues modified in C-9 position was investigated by molecular docking and molecular dynamics (MD) simulation methods. Methyl-α-Neu5Ac analogues were docked against cholera toxin (CT) B subunit protein and MD simulations were carried out for three Methyl-α-Neu5Ac analogue-CT complexes (30, 10 and 10 ns) to estimate the binding activity of cholera toxin-Methyl-α-Neu5Ac analogues using OPLS_2005 force field. In this study, direct and water mediated hydrogen bonds play a vital role that exist between the methyl-α-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ)-cholera toxin active site residues. The Energy plot, RMSD and RMSF explain that the simulation was stable throughout the simulation run. Transition of phi, psi and omega angle for the complex was calculated. Molecular docking studies could be able to identify the binding mode of methyl-α-Neu5Ac analogues in the binding site of cholera toxin B subunit protein. MD simulation for Methyl-α-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ), Methyl-α-9-N-acetyl-9-deoxy-9-amino-Neu5Ac and Methyl-α-9-N-biphenyl-4-acetyl-deoxy-amino-Neu5Ac complex with CT B subunit protein was carried out, which explains the stable nature of interaction. These methyl-α-Neu5Ac analogues that have computationally acceptable pharmacological properties may be used as novel candidates for drug design for cholera disease.

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Acknowledgments

The authors acknowledge the financial support given by SERB (Science and Engineering Research Board, DST) Ref No. (SR/FT/LS-157/2009), Govt. of India, New Delhi.

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Authors and Affiliations

  1. Department of Nano Science and Technology, Tamil Nadu Agricultural University, Coimbatore, 641003, Tamil Nadu, India

    D. Jeya Sundara Sharmila

  2. Department of Bioinformatics, Karunya University, Karunya Nagar, Coimbatore, 641114, Tamil Nadu, India

    J. Jino Blessy

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Correspondence to D. Jeya Sundara Sharmila.

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Blessy, J.J., Sharmila, D.J.S. Molecular modeling of methyl-α-Neu5Ac analogues docked against cholera toxin - a molecular dynamics study. Glycoconj J 32, 49–67 (2015). https://doi.org/10.1007/s10719-014-9570-6

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