Short Report J Mol Genet Med (January 2009), 3(1), 133-142 doi: jmgm Published online: 26 November 2008 Full Text: (html | pdf ~902kb | refs) Ab initio base fragment molecular orbital studies of influenza viral hemagglutinin HA1 full-domains in complex with sialoside receptors Toshihiko Sawada †,‡,*, Tomohiro Hashimoto §, Hiroaki Tokiwa †,¥, Tohru Suzuki ¶, Hirofumi Nakano ƒ, Hideharu Ishida ¢, Makoto Kiso †,¢ ,Yasuo Suzuki †,‡,Œ,* † Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan‡ College of Life and Health Sciences, Chubu University, Kasugai, Aichi 487-8501, Japan § Faculty of Regional Studies, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan ¥ Department of Chemistry, Faculty of Science, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Tokyo 171-8501, Japan ¶ The United Graduate School of Agricultural Science, Gifu University, Japan ƒ Department of Chemistry, Aichi University of Education, Kariya, Aichi 448-8542, Japan ¢ Department of Applied Bioorganic Chemistry, Gifu University, Japan Œ Japan and Global COE Program for Innovation in Human Health Sciences, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka 422-8526, Japan *Correspondence to: Toshihiko Sawada, Email: sawada-t@aist.go.jp, Tel: +81 29 8613298, Fax: +81 29 8613171; Yasuo Suzuki, Email: suzukiy@isc.chubu.ac.jp, Tel/Fax: +81 568 516391 Received: 26 July 2008, Revised: 28 October 2008, Accepted: 30 October 2008 © Copyright The Authors ----------------------------------------------------------------------------------------------------------------- ABSTRACT Mutations in avian influenza A viral hemagglutinin HA1 domain may alter the binding specificity of HA for α-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 Neu5Acα(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 α2-3 receptor more strongly than to human α2-6 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 α2-3 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. KEYWORDS: Virus host range, sialosaccharide, lectin, ab initio, FMO, binding energy, interfragment interaction energy, second-order Møller–Plesset perturbation ----------------------------------------------------------------------------------------------------------------- Privacy | Disclaimer |