We have studied the substrate selectivity of sulfotransferase SULT1A3 by identifying significant protein-ligand interactions in the active site through modeling. Sulfotransferases are involved in the regulation of neurotransmitters and hormones as well as the metabolism of drugs and other xenobiotics. Eight dopaminergic ligands and resveratrol are the focus of this study and with electronic interaction energies calculated using MP2 and M062X with the 6-311+G* basis set. Optimizations and calculations were performed in three ways: <i>in vacuo</i> with rigid amino acid residue side chains, with implicit solvation with rigid amino acid residue side chains, and with implicit solvation by water with relaxed amino acid residue side chains. The calculations indicate that using an implicit solvent and relaxed active site results in stronger binding in ligand interaction energies. The dopaminergic ligand with the strongest interaction energy of the ligands studied is 6-carboxydopamine; three other ligands—6-cyanodopamine, 6-hydroxydopamine, and 6-bromodopamine—exhibit stronger interaction energies than the endogenous ligand, dopamine.

Effects of implicit solvation, relaxed amino acid side chains, and point mutations on the MP2 and DFT calculations of ligand-protein structure and interaction energies of dopaminergic ligands in the SULT1A3 enzyme active site

249th National Meeting (2015)

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