Interaction of Cyclohexanediones with Acetyl Coenzyme-A Carboxylase and an Artificial Target-Site Antibody Mimic: A Comparative Molecular Field Analysis

Similarities and differences between steric and electrostatic potentials of a monoclonal-antibody-based surrogate of a herbicide target-site and its in vitro enzyme target were investigated using three-dimensional quantitative structure−activity relationship comparative molecular field analysis (3D-QSAR CoMFA). Two separate, five-component, partial least squares CoMFA models were developed to compare the interaction of cyclohexanedione herbicides with their target site, acetyl coenzyme-A carboxylase (ACCase; EC 6.4.1.2) and a cyclohexanedione pharmacophore-specific monoclonal antibody (mAb A). On the basis of CoMFA models, similarities in steric and electrostatic requirements around position 2 of the binding site for the oxime functional group of the cyclohexanedione molecule appear to be crucial for interaction of the herbicide with both ACCase and mAb A. These similarities explain the observed quantitative relationship between binding of cyclohexandedione herbicides to ACCase mAb A. Furthermore, these results support the production and use of mAb-based surrogates of pesticide targets as screening tools in pesticide discovery programs. Keywords: Monoclonal; cyclohexanedione herbicides; ACCase; CoMFA