This investigation was performed to present the construction of rough homology models, the refinement using molecular methanics and molecular dynamics, and the optimization of these models into “antagonist-bound” models using training set docking for α_1A-, α_1B- and α_1D-AR models. A test set consisting of 18 molecules was then docked into to obtained “antagonist-bound” models using FRED program. The docking scores and experimental affinities were analyzed by linear regression to obtain a good correlation. Consequently, this work highlights the rational construction for “antagonist-bound”α_1A-, α_1B- and α_1D-AR models. The knowledge of these models can be used for virtual screening to discover more novel potential molecules.

Key words: adrenoceptor, antagonist, homology model, molecular modeling, docking