Simulação computacional do mecanismo catalítico da enzima catecol o-metiltransferase

Abstract

Methyl transfer reactions are very important in biological systems, the enzyme catechol O-methyltranferase catalyzes a transfer reaction of a methyl group of the co-substrate S-adenosylmethionine to dopamine. This disease is related to a Parkinson's disease that is a neurodegenerative disease that affects 7 to 10 million people of the world population, mainly a parcel over 60 years. Due to the importance of the reaction catalyzed by this enzyme, computational tools in conjunction with quantum mechanics methods were used to study the mechanism of reaction of the methyl transfer of S-adenosylmethionine to dopamine. In this study, the presence or not of Mg2+ in the reaction and changes in dopamine structure for catechol and phenol were taken into account in order to propose a quantum region more suitable for future non-enzymatic simulation work. The methods used in the PM6 semi-present method, the ab initio DFT and the MP2 correlation. The methods used include PM6 semiempirical method, ab initio DFT and perturbation MP2, where the first method was highlighted in the description of all reactions studied. The reaction with the catechol in the solvent had the following values of energy barriers: 18.62 kcal/mol (PM6); 9.91 kcal/mol (DFT); 14.44 kcal/mol (MP2). The presence of the Mg2+ ion in the same reaction with the catechol showed the following energy barrier values: 24.55 kcal/mol (PM6); 15.99 kcal/mol (DFT); 17.39 kcal/mol (MP2). The PCM solvation model was used to study a reference reaction in the enzymatic system and to analyze how energy barriers of the reaction in water and with barriers obtained in the gas.