Li Minyong, Wang Binghe
Department of Chemistry and Center for Biotechnology and Drug Design, Georgia State University, Atlanta, 30302-4098, USA.
Biochem Biophys Res Commun. 2006 Sep 1;347(3):662-8. doi: 10.1016/j.bbrc.2006.06.179. Epub 2006 Jul 10.
For influenza H5N1 hemagglutinin, a switch from SA-alpha-2, 3-Gal to SA-alpha-2, 6-Gal receptor specificity is a critical step leading to the conversion from avian-to-human to human-to-human infection. Therefore, the understanding of the binding modes of SA-alpha-2, 3-Gal and SA-alpha-2, 6-Gal to H5N1 hemagglutinin will be very important for the examination of possible mutations needed for going from an avian to a human flu virus. Based on the available H5N1 hemagglutinin crystal structure, the binding profiles between H5N1 hemagglutinin and two saccharide ligands, SA-alpha-2, 3-Gal and SA-alpha-2, 6-Gal, were investigated by ab initio quantum mechanics, molecular docking, molecular mechanics, and molecular dynamics simulations. It was found that SA-alpha-2, 3-Gal has strong multiple hydrophobic and hydrogen bond interactions in its trans conformation with H5N1 hemagglutinin, whereas the SA-alpha-2, 6-Gal only shows weak interactions in a different conformation (cis type).
对于甲型H5N1流感病毒血凝素而言，从结合唾液酸α-2,3-半乳糖（SA-α-2,3-Gal）受体特异性转变为结合唾液酸α-2,6-半乳糖（SA-α-2,6-Gal）受体特异性，是该病毒从禽传人感染转变为人传人的关键步骤。因此，了解SA-α-2,3-Gal和SA-α-2,6-Gal与H5N1血凝素的结合模式，对于研究禽流感病毒转变为人类流感病毒所需的可能突变非常重要。基于现有的H5N1血凝素晶体结构，通过从头算量子力学、分子对接、分子力学和分子动力学模拟，研究了H5N1血凝素与两种糖类配体SA-α-2,3-Gal和SA-α-2,6-Gal之间的结合情况。研究发现，SA-α-2,3-Gal在反式构象中与H5N1血凝素存在强烈的多重疏水和氢键相互作用，而SA-α-2,6-Gal仅在不同构象（顺式）中表现出较弱的相互作用。
