Role of the Key Mutation in the Selective Binding of Avian and Human Influenza Hemagglutinin to Sialosides Revealed by Quantum-Mechanical Calculations
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- 作者：Toshihiko Sawada ; Dmitri G. Fedorov ; Kazuo Kitaura
- 刊名：Journal of the American Chemical Society
- 出版年：2010
- 出版时间：December 1, 2010
- 年：2010
- 卷：132
- 期：47
- 页码：16862-16872
- 全文大小：343K
- 年卷期：v.132,no.47(December 1, 2010)
- ISSN：1520-5126
文摘
The selective binding between avian and human influenza A viral hemagglutinins (HA) subtype H3 and Neu5Acα2-3 and α2-6Gal (avian α2-3, human α2-6) is qualitatively rationalized by the fragment molecular orbital (FMO) method. We suggest a general model of analyzing protein−ligand interactions based on the electrostatic, polarization, dispersion, and desolvation components obtained from quantum-mechanical calculations at the MP2/6-31G(d) level with the polarizable continuum model of solvation. The favorable avian H3 (A/duck/Ukraine/1963)−avian α2-3 binding arises from the hydrophilic interaction between Gal-4 OH and side-chain NH2CO on Gln226, which is supported by the intermolecular hydrogen-bond network to the 1-COO group on Neu5Ac moiety. A substitution of Gln226Leu in the avian H3 HA1 domain increases the binding affinity to human α2-6 due to the Leu226···human α2-6 dispersion with a small entropic penalty during the complex formation. The remarkable human H3 (A/Aichi/2/1968)−human α2-6 binding is not governed by the Ser228-OH···OH-9 Neu5Ac hydrogen bond. These fragment-based chemical aspects can help design monovalent inhibitors of the influenza viral HA−sialoside binding and the simulation studies on the viral HAs−human α2-6 binding.