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 () 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 ( = 1.53 µM) and DMHBP on DSZB enzyme ( = 3.87 µM) was most marked. The inhibitory effect of HBP on DSZC and DSZB enzymes was moderate due to of 6.36 and 7.93 µM, respectively. The inhibition effect of DMHBP on the DSZA enzyme was insignificant due to high of 53.6 µM. In summary, higher stability of enzyme-substrate complexes and strong inhibition by DMHBPS and DMHBP (due to very low ) contribute to slower biodesulfurization of 4,6-DMDBT as compared to DBT.