A Computational Study of the Promiscuity of the SAM-Dependent Methyltransferase AtHTMT1.

A two-pronged computational approach was taken to study the promiscuity of the SAM-dependent methyl transferase AtHTMT1 from thale cress with several nucleophiles (Cl, Br, I, NCO, NCS). First, enzyme-free methyl transfer reactions were studied with M05/6-311+G(2d,p) DFT calculations and electrostatic continuum models (PCM/SMD) for various chemical environments. Second, QM/MM MD simulations with semiempirical Hamiltonians (PM7, PM6-D3, AM1, PM6-D3H4) and the AMBER 14SB force field were used to study the enzyme catalyzed reaction .