CONICET | Buscador de Institutos y Recursos Humanos

Understanding of the biological behavior of different L-R complexes requires determiningthe conformational and electronic aspects of both the small ligand as well as the bindingsite of its receptor. Here we report the conformational and electronic behavior ofdopamine (DO) interacting at the active site of the D2 dopamine receptor (D2DR). Theselection of this molecular target is due to two main reasons: it is a molecular target ofgreat importance for medicinal chemistry and very useful structural information hasbeen recently reported due to the D2DR has been crystallized. Different computationaltechniques have been used in combination in this study. In this way, dockingcalculations, molecular dynamics simulations and quantum mechanical calculations havebeen performed. Moreover, the different molecular interactions of the complexes wereevaluated in detail using two techniques: QTAIM (Quantum Theory of Atoms inMolecules) and NMR nuclear magnetic shielding constants calculations.Our study goes much further than any previously done, since for the first time we havebeen able to obtain and report the complete conformational potential energy surface(PES) for DO in its binding pocket. Analysis of the complete PES is the mostcomprehensive way to understand the conformational behavior of a ligand such as DO,which possesses two rotatable bonds, since it is possible to locate all critical points onthe surface and even see its different conformational inter-conversion paths.Our study indicates that seven different conformations of DO are the most relevant. Fromthese seven ones, two are those that could be considered as the biologically relevantconformations of DO. On the other hand, the most important molecular interactions thatstabilize these molecular complexes are those with Asp80, Val81, Cys84, Thr85, Ser159,Ser160, Ser163, Phe164 and Tyr403.