Molecular Docking and 3D-QSAR Studies on a Series of Benzenesulfonamide Derivatives as a Hepatitis B Virus Capsid Assembly Inhibitor

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: r(2) = 0.998, q(2)= 0.625, r(pred)(2)= 0.837; CoMSIA: r(2)= 0.987, q(2) = 0.645, r(pred)(2)= 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.

Automated summary

This paper presents a study on the structure-activity relationship of a series of HBV capsid assembly inhibitors using 3D-QSAR methods. The models show high predictive ability and the binding mode between compounds and receptor protein was explored through molecular docking, confirming the relationship revealed by the QSAR models.