Abstract Computer models of hemagglutinins from the H3N2 and H7N9 influenza viruses were developed to study structural organization and dynamic characteristics of the binding site for the conformational rearrangement inhibitors. The metadynamics was used to map the binding site free energy and to define the volume of its most energetically favorable states. It was demonstrated by simulation of the umifenovir (Arbidol) interaction with hemagglutinin that ligand binding requires an increase in the binding site volume and deformation of its most energetically favorable state. We also identified amino acid residues directly involved in the ligand binding that determine the binding efficiency, as well as the dynamic behavior of the binding site. The revealed features of the binding site structural organization of the influenza virus hemagglutinin should be taken into account when searching for new antiviral drugs capable to modulate its functional properties.

中文翻译：

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H3N2和H7N9流感病毒血凝素构象重排抑制剂结合位点的结构组织和动态特征

摘要 开发了 H3N2 和 H7N9 流感病毒血凝素的计算机模型，以研究构象重排抑制剂结合位点的结构组织和动态特征。元动力学用于绘制结合位点自由能并定义其最有利的状态的体积。通过模拟乌米诺韦 (Arbidol) 与血凝素的相互作用证明，配体结合需要增加结合位点体积并使其最有利的状态变形。我们还鉴定了直接参与决定结合效率的配体结合的氨基酸残基，以及结合位点的动态行为。