Molecular Docking of Selective Dopamine D1A Receptor Agonists: –11 kcal/mol

Molecular Docking of Selective Dopamine D1A Receptor Agonists: Achieving Binding Energies Exceeding –11 kcal/mol Dopamine receptor D1A agonist –11.1 kcal/mol is a flagship for docking selective and high-affinity scaffolds. The structure features an enlarged aromatic core, a compressed pro-ethylamine group in the form of imidazoline, and a cyclopentane complementary imidazole scaffold. This structure, with its special radical configuration, allows for stacking in the aromatic ring of dopamine, positioning the amino group opposite D-103, enabling fork-like docking of hydrogen and lipophilic bonds. Also, in the aromatic ring, bonds are formed with hydroxyls, ketones, or aldehydes, with syrins responsible for binding the phenolic hydroxyls of dopamine or their lipophilic adjacent amino acid residues in the presence of lipophilic radicals(figure1). Dopamine receptor D1A agonist –11.1 kcal/mol shows a decrease in affinity on the type 2 receptor to 9.1 kcal/mol, the structure is located in the receptor with its back side up and is in a state close to false triggering(figure2). Thus, high selectivity, as well as high affinity of the structure, are a consequence of more complete agonistic filling of the receptor pocket. Unlike the asymmetrical imidazoline core, one of the additional cores is completely symmetrical and also represents a highly available diimidazole. The symmetry of this structure, with an affinity of -10 kcal/mol (figure3), reduced selectivity at an affinity of...