Sialic Acid Recognition of the Pandemic Influenza 2009 H1N1 Virus: Binding Mechanism Between Human Receptor and Influenza Hemagglutinin

Kaori      Fukuzawa; Katsumi      Omagari; Katsuhisa      Nakajima; Eri      Nobusawa; Shigenori      Tanaka

Abstract

Quantum mechanical fragment molecular orbital calculations have been performed for receptor binding of the hemagglutinin protein of the recently pandemic influenza 2009 H1N1 (2009/HIN1pdm), A/swine/Iowa/1930, and A/Puerto Rico/8/1934 viruses to α2-6 linked sialyloligosaccharides, as analogs of human receptors. The strongest receptor binding affinity was observed for the 2009/H1N1pdm. The inter-fragment interaction energy analysis revealed that the amino acid mutation of 2009/H1N1pdm, Ser145Lys, was a major cause of such strong binding affinity. Strong ionic pair interaction between the sialic acid and Lys145 was observed only in the 2009/H1N1pdm, in addition to the hydrogen bond between the sialic acid and Gln226 observed in all the HAs. Therefore, pandemic 2009/H1N1pdm has been found to recognize the α2-6 receptor much stronger than the 1930-swine and 1934-human.

Keywords: Pandemic influenza 2009 H1N1 virus (2009/H1N1pdm), influenza hemagglutinin (HA), sialic acid recognition, fragment molecular orbital (FMO) method, quantum mechanical calculation, sialo-sugar chain, sialyloligosaccharides, FMO, IFIE, RMSD, HF, Generalized Born (GB), molecular mechanics (MM), LSTc, NCBI Influenza virusPandemic influenza 2009 H1N1 virus (2009/H1N1pdm), influenza hemagglutinin (HA), sialic acid recognition, fragment molecular orbital (FMO) method, quantum mechanical calculation, sialo-sugar chain, sialyloligosaccharides, FMO, IFIE, RMSD, HF, Generalized Born (GB), molecular mechanics (MM), LSTc, NCBI Influenza virus