Studying the catechol binding cavity in comparative models of human dopamine D-2 receptor
Obtaining more structural information of human dopamine D-2 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 D-2 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 beta-adrenergic receptors, might also take place in the human D-2 receptor during its interaction with agonist ligands. (C) 2010 Elsevier Inc. All rights reserved.
comparative modeling conformational changes g protein coupled receptor agonist binding cavity ligand screening