Comparative analysis of biodesulfurization of dibenzothiophene (DBT) and 4,6-dimethyl dibenzothiophene (4,6-DMDBT) by 4S pathway using molecular simulations.

In this paper, we have analyzed biodesulfurization of dibenzothiophene (DBT) and 4,6-dibenzothiophene (4,6-DMDBT) by 4S metabolic pathway using molecular simulations. Docking analysis revealed lower binding energies and inhibition constants (K_i) for 4,6-DMDBT and its metabolic intermediates with DSZ enzymes than DBT and its intermediates. The complexes of substrate and its metabolites with DSZ enzymes had higher stability for 4,6-DMDBT than DBT owing to lower RMSF values than apoprotein. The docking analysis revealed affinity of the inhibitors HBPS and HBP (for DBT) and DMHBPS and DMHBP (for 4,6-DMDBT) toward DSZ enzyme due to negative binding energies. Molecular dynamics simulations showed stability of several enzyme-inhibitor complexes. The inhibitory effect of DMHBPS on DSZC enzyme (K_i = 1.53 µM) and DMHBP on DSZB enzyme (K_i = 3.87 µM) was most marked. The inhibitory effect of HBP on DSZC and DSZB enzymes was moderate due to K_i of 6.36 and 7.93 µM, respectively. The inhibition effect of DMHBP on the DSZA enzyme was insignificant due to high K_i of 53.6 µM. In summary, higher stability of enzyme-substrate complexes and strong inhibition by DMHBPS and DMHBP (due to very low K_i) contribute to slower biodesulfurization of 4,6-DMDBT as compared to DBT.