Molecular dynamics studies of human receptor molecule in hemagglutinin of 1918 and 2009 H1N1 influenza viruses

Molecular dynamics (MD) simulations were carried out to study the behavior of human receptor molecule in the hemagglutinin (HA) of 1918 and 2009 H1N1 influenza viruses respectively. The 2009 HA model was obtained by virtually mutating the 1918 HA crystal structure based on A/Mexico City/MCIG01/2009(H1N1) segment 4 sequence. We found that human receptor molecule has no binding preference between the 2009 HA and the 1918 HA. In addition, among the four sugar moieties in the human receptor molecule, sialic acid contributes the most to the electrostatic and non-polar interaction energy during binding. Furthermore, the hydrogen bonds between sialic acid and the surrounding residues in 1918 HA are preserved in 2009 HA. We also found that the mutated residues contribute to a more favorable binding of hemagglutinin to the human receptor molecule.

[1]  Gabriele Neumann,et al.  Emergence and pandemic potential of swine-origin H1N1 influenza virus , 2009, Nature.

[2]  Wei Zhang,et al.  A point‐charge force field for molecular mechanics simulations of proteins based on condensed‐phase quantum mechanical calculations , 2003, J. Comput. Chem..

[3]  Marwen Naïm,et al.  Molecular dynamics-solvated interaction energy studies of protein-protein interactions: the MP1-p14 scaffolding complex. , 2008, Journal of molecular biology.

[4]  Imran Siddiqi,et al.  Solvated Interaction Energy (SIE) for Scoring Protein-Ligand Binding Affinities, 1. Exploring the Parameter Space , 2007, J. Chem. Inf. Model..

[5]  Xue‐Wei Liu,et al.  Dual native chemical ligation at lysine. , 2009, Journal of the American Chemical Society.

[6]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[7]  J. Aqvist,et al.  A new method for predicting binding affinity in computer-aided drug design. , 1994, Protein engineering.

[8]  Libo Dong,et al.  Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. , 2009, The New England journal of medicine.

[9]  Xue‐Wei Liu,et al.  A convenient synthesis of pseudoglycosides via a Ferrier-type rearrangement using metal-free H3PO4 catalyst , 2009 .

[10]  Karl Nicholas Kirschner,et al.  GLYCAM06: A generalizable biomolecular force field. Carbohydrates , 2008, J. Comput. Chem..

[11]  J. Skehel,et al.  Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. , 2000, Annual review of biochemistry.

[12]  J. Skehel,et al.  Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957 , 2009, Proceedings of the National Academy of Sciences.

[13]  R. Compans,et al.  Characterization of temperature sensitive influenza virus mutants defective in neuraminidase. , 1974, Virology.

[14]  James E. Crowe,et al.  Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus , 2010, Science.

[15]  Xue‐Wei Liu,et al.  Microwave-enhanced one-pot synthesis of diversified 3-acyl-5-hydroxybenzofurans. , 2007, Journal of combinatorial chemistry.

[16]  H. Berendsen,et al.  Molecular dynamics with coupling to an external bath , 1984 .

[17]  Hideo Goto,et al.  In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses , 2009, Nature.

[18]  J. Skehel,et al.  The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. , 1987, Annual review of biochemistry.

[19]  G. Ciccotti,et al.  Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes , 1977 .