Binding of the neuroleptic drug haloperidol to a monoclonal antibody: Refinement of the binding site molecular model using canonical structures

The ligand binding site of a monoclonal antibody (185), which binds the neuroleptic drug haloperidol, has been modelled using canonical structures and energy minimization techniques. This refined modelling protocol has allowed us to predict the variable region loop conformations. Three key residues, H:50(W), H:100a(D) and L:96(Y) appear to create the basis of the electrostatic, pi-pi stacking interactions and hydrogen bonding required for the high affinity binding site characteristics present in this antibody. The use of computer-aided graphics techniques and appropriate three-dimensional modelling permits inspection of the predicted molecular recognition features of the ligand binding site.