Abstract

In this present study, we have determined the crystal structure of 2-acetamidophenyl acetate (2-AAPA) commonly used as influenza neuraminidase inhibitor, to analyze the polymorphism. Molecular docking and molecular dynamics have been performed for the 2-AAPA-neuraminidase complex as the ester-derived benzoic group shows several biological properties. The X-ray diffraction studies confirmed that the 2-AAPA crystals are stabilized by N–H···O type of intermolecular interactions. Possible conformers of 2-AAPA crystal structures were computationally predicted by ab initio methods and the stable crystal structure was identified. Hirshfeld surface analysis of both experimental and predicted crystal structure exhibits the intermolecular interactions associated with 2D fingerprint plots. The lowest docking score and intermolecular interactions of 2-AAPA molecule against influenza neuraminidase confirm the binding affinity of the 2-AAPA crystals. The quantum theory of atoms in molecules analysis of these intermolecular interactions was implemented to understand the charge density redistribution of the molecule in the active site of influenza neuraminidase to validate the strength of the interactions.

Communicated by Ramaswamy H. Sarma

摘要

在本研究中，我们确定了常用作流感神经氨酸酶抑制剂的乙酸 2-乙酰氨基苯酯 (2-AAPA) 的晶体结构，以分析其多态性。已经对 2-AAPA-神经氨酸酶复合物进行了分子对接和分子动力学，因为酯衍生的苯甲酸基团显示出多种生物学特性。X射线衍射研究证实，2-AAPA晶体通过N-H···O型分子间相互作用稳定。从头算计算预测了 2-AAPA 晶体结构的可能构象异构体方法并确定了稳定的晶体结构。实验和预测晶体结构的 Hirshfeld 表面分析展示了与二维指纹图相关的分子间相互作用。2-AAPA 分子对流感神经氨酸酶的最低对接分数和分子间相互作用证实了 2-AAPA 晶体的结合亲和力。实施了这些分子间相互作用的分子分析中的原子量子理论，以了解分子在流感神经氨酸酶活性位点的电荷密度重新分布，从而验证相互作用的强度。

由 Ramaswamy H. Sarma 传达