Theoretical investigation on the binding specificity of fluorinated sialyldisaccharides Neu5Acα(2–3)Gal and Neu5Acα(2–6)Gal with influenza hemagglutinin H1 – A Molecular Dynamics Study

ABSTRACT

In the present study, the hydroxyl groups at the C4 and C7 positions of sialic acid and C6 position of galactose in Neu5Acα(2–3)Gal (N23G) and the hydroxyl groups at the C8 position of sialic acid and C3 and C4 positions of galactose in Neu5Acα(2–6)Gal (N26G) were substituted with fluorine atoms, respectively. Molecular dynamics simulations of 100 ns duration were carried out to investigate the structural and dynamical behavior of H1 bound with the tri-fluorinated N23G and N26G (FN23G and FN26G). Based on energy analysis, it was concluded that FN26G should be a better binder for hemagglutinin (H1) than FN23G and it might act as an inhibitor for influenza.

KEYWORDS:

• fluorinated sialyldisaccharide
• molecular dynamics
• hemagglutinin
• binding specificity
• influenza A virus
• inhibitor design

Acknowledgements

VM and PP acknowledge the DBT, India-AIST, Japan bilateral project for Junior Research Fellowship (BT/IC/JAPAN(BI)/02/2010). All the authors acknowledge the use of DBT funded Bioinformatics Infrastructure Facility (BIF) hosted at the Department of Biotechnology, Manonmaniam Sundaranar University (BT/BI/25/049/2012). VM acknowledges Supercomputing Facility – VIRGO, IIT Madras for computational support. Dr. KV and Dr. MG acknowledge the DBT-Government of India, for projects funding (BT/PR12267/BID/7/506/2014 and BT/PR13410/BID/7/536/2015). VM acknowledges Dr. C. Ramakrishnan, Post Doctoral Fellow, Department of Biotechnology, IIT Madras for helping in simulations and data regarding the same. VM acknowledges Dr. T. R. K Priyadarzini for fruitful discussions.