Ab initio base fragment molecular orbital studies of influenza viral hemagglutinin HA1 full-domains in complex with sialoside receptors
- *Corresponding Author:
- Toshihiko Sawada
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Received date: 26 July 2008, Revised date: 28 October 2008, Accepted date: 30 October 2008, Published online 26 November 2008
© Copyright The Authors:This is an open access article, published under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/2.0/uk/). This license permits non- commercial use, distribution and reproduction of the article, provided the original work is appropriately acknowledged with correct citation details.
Mutations in avian influenza A viral hemagglutinin HA1 domain may alter the binding specificity of HA for F-sialosaccharide receptors, shifting the virus’s host range from birds to humans. The amino acid mutations can occur at the sialoside binding site, as well as the antigenic site, far from the binding site. Thus, a theoretical study involving the in silico prediction of HA-sialosaccharide binding may require quantum chemical analysis of HA1 full domain complexed with sialosides, balancing a computational cost with model size of HA1-sialoside complex. In addition, there is no insight to relationship between the model size of HA1-sialoside complex and its binding energy. In this study, H3 subtype HA1 full domains complexed with avian- and human-type Neu5AcF(2-3 and 2-6)Gal receptor analogs was investigated by ab initio based fragment molecular orbital (FMO) method at the level of second-order Møller–Plesset perturbation (MP2)/6- 31G. Using this approach, we found avian H3 HA1 to bind to avian F2-3 receptor more strongly than to human F2-6 receptor in gas phase, by a value of 15.3-16.5 kcal/mol. This binding benefit was larger than that in the small model complex. Analysis of the interfragment interaction energies (IFIEs) between Neu5Ac-Gal receptor and amino acid residues on the full domain of H3 HA1 also confirmed the higher avian H3-avian F2-3 binding specificity. It was particularly important to evaluate the IFIEs of amino acid residues in a 13Å radius around Neu5Ac-Gal to take account of long-range electrostatic interactions in the larger HA1- sialoside complex model. These results suggest suitable size of HA1-sialoside complex is significant to estimate HA1-sialoside binding energy and IFIE analysis with FMO method.