Studying the catechol binding cavity in comparative models of human dopamine D2 receptor

Obtaining more structural information of human dopamine D2 receptor may help in the design of better therapeutic agents against diseases such as Parkinsons. In this study attempts have been made to develop a functional model for the catechol binding site of the human dopamine D2 receptor, with two primary models being postulated based on the presence of a disulfide bridge in the second extracellular loop. The models have been subjected to subsequent molecular dynamics simulation and receptor based virtual screening of catechol structures. During steady state of the simulations, representative models with the reduced disulfide bridge were more capable of discriminating between active and inactive catechol structures. It is postulated that similar conformational changes of the second extracellular loop observed in 5-HT4 and β-adrenergic receptors, might also take place in the human D2 receptor during its interaction with agonist ligands.

Figure optionsDownload high-quality image (150 K)Download as PowerPoint slideResearch highlights▶ We have made two models for human dopamine D2 receptor. ▶ The models were different based on the presence of a disulfide bridge. ▶ The two modeled were undertaken molecular dynamics simulation and docking studies. ▶ The model with the reduced disulfide bridge was a more predictive one.