Abstract

In this paper, a three-dimensional quantitative structure-activity relationship (3D-QSAR) namely CoMFA and CoMSIA has been carried out on a series (43 compounds) of capsid assembly inhibitors on N-phenyl-3-sulfamoyl-benzamide-based. The statistical parameters from the models (CoMFA: r² = 0.998, q² = 0.625, r² _pred = 0.837; CoMSIA: r² = 0.987, q² = 0.645, r² _pred = 0.698) indicate that the data are well fitted and have high predictive ability. Molecular docking was employed to explore the binding mode between these compounds and the receptor protein, as well as help understand the structure-activity relationship revealed by CoMFA and CoMSIA. Contour maps of the QSAR models were generated and validated by molecular docking study. The final models of CoMFA/CoMSIA and molecular docking could be useful for the design and development of novel potent HBV capsid assembly inhibitors.

摘要

在本文中，在一系列基于N-苯基-3-氨磺酰基-苯甲酰胺的衣壳装配抑制剂（43种化合物）上进行了三维定量构效关系（3D-QSAR），即CoMFA和CoMSIA 。来自模型的统计参数（CoMFA：r ² = 0.998，q ² = 0.625，r ² _pred = 0.837; CoMSIA：r ² = 0.987，q ² = 0.645，r ² _pred = 0.698）表示数据拟合良好且具有较高的预测能力。分子对接用于研究这些化合物与受体蛋白之间的结合方式，并有助于理解CoMFA和CoMSIA揭示的结构活性关系。通过分子对接研究生成并验证了QSAR模型的等高线图。CoMFA / CoMSIA和分子对接的最终模型可用于设计和开发新型有效的HBV衣壳装配抑制剂。