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

ABSTRACT: 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 in silico. The combination of the DFT and MD results shows that reactant desolvation generally accelerates the reaction, but it cannot explain the selectivity of the enzyme. The critical

SUBMITTER: Lankau T 

PROVIDER: S-EPMC9026064 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature