Acetaminophen is commonly used analgesic. Cresols such as p-cresol, o-cresol, and m-cresol can compete with acetaminophen for metabolism. We have applied MP2 and DFT methods to study the interaction of acetaminophen and these cresol analogues with the active site of aryl sulfotransferase, which is involved in the sulfation-pathway of acetaminophen metabolism. Docking and BHandHLYP optimization were used to find the structures of the ligand-protein complexes assuming a static active site. Interaction energies between the ligands and each of the amino acids in the active site were calculated MP2 and SVWN/6-311+g*. Optimizations were performed to allow flexibility of the amino-acid-residues in the active site and interaction energies were calculated for these complexes as well. We can thus offer predictions as to how competitive the cresol analogues are with acetaminophen for metabolism. In recent work we have studied mutant versions of the active site with p-nitrophenol to determine the change in ligand-binding.

MP2 calculations of interaction energies between acetaminophen and acetaminophen analogs in aryl sulfotransferase

243rd National Meeting (2012)

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