Computational Study of the Degradation of S-Adenosyl Methionine in Water

Abstract

The degradation of S-adenosyl methionine (SAM) to homoserine-γ-lactone (HSL) and methyltioadenine (MTA) in water is studied with MD simulations. The AM1 Hamiltonian is used for the quantum part and the flexible AMBER force field for the H₂O molecules. The MD simulations predict the free energy barrier for the degradation reaction to be between 109 and 112 kJ mol^-1 and an overall gain in free energy of -26 kJ mol^-1. The high barrier and the low energy gain of this reaction can be linked to interactions among the carboxylate group of the SAM molecule and solvent H₂O molecules, which are not observed on the product side. Hence, the H₂O molecules effectively slow down the reaction that otherwise would be much faster.