The Effects of Ligand Deprotonation on the Binding Selectivity of the Phenylalanine Hydroxylase Active Site

We report promising novel catechols that do not inhibit this enzyme. Results show deprotonation of the ligands by the active site can strongly affecting their binding strength, thus the pKas for all novel ligands were calculated and are reported.Graphical abstractNew family of molecules (PG-X) that do not inhibit Phenylalanine Hydroxylase, thus making them possible drug candidates for raising levels of dopamine in the brain. Shown above is PG-OH, which has the weakest interaction energy when optimized in the Phenylalanine Hydroxylase active site. Optimization is performed with M062X/6-31G, implicit solvation, and relaxed amino acid side chains.
Source: Computational and Theoretical Chemistry - Category: Chemistry Source Type: research