Molecular Virtual Screening Studies of Herbicidal Sulfonylurea Analogues Using Molecular Docking and Topomer CoMFA Research

Abstract

A three-dimensional quantitative structure-activity relationship (3D-QSAR) model of 45 sulfonylurea herbicidals is established using the Topomer comparative molecular field analysis (Topomer CoMFA). The results show that correlation coefficient (q²), non-cross-validation correlation coefficient (r²), and external validation (Q_ext²) are 0.884, 0.908, and 0.857 respectively. The biological evaluation demonstrates that the obtained model has the excellent external predictive ability and good estimation stability. The methodology of the fragment-based drug design is also applied to design new sulfonylurea herbicides using the Topomer Search technology. Compound 11 with the highest activity is chosen as the template molecule. By adding three substitutional groups selected from the ZINC database to the template molecule, 36 new compounds with an activity more than that of the template molecule are obtained. The template molecular and designed compounds are used to explore the binding relationship of the ligands with the receptor protein in molecular docking. The result shows that hydrogen bonding interactions form between the ligands and amino acid residues.