Challenging Dissimilatory Adenosine 5'-Phosphosulfate (APS) Reductase with Assimilatory APS Reductase Inhibitors by Docking and Molecular Dynamics Simulations: A Computational Study

Dissimilatory adenosine 5’-phosphosulfate reductase (APSrAB) is a metalloenzyme of the metabolic pathway of sulfate-reducing microorganisms, which generates H2S in oil production wells, causing losses in the oil industry. A set of 32 compounds derivatives of adenosine 5’-phosphosulfate (APS), previously evaluated as inhibitors of the assimilatory adenosine 5’-phosphosulfate reductase (APSr), were challenged in this current work by in silico molecular docking and molecular dynamics (MD) techniques as potential inhibitors of the APSrAB (APS is substrate of both enzymes). From this set, 20 compounds showed the highest affinity by the APSrAB (tendency to remain in the binding site pointed out by the docking experiments). The residues of the active site (71-398 region) had hydrogen bonds with a lifetime of more than 10.00% (mainly Arg265). They were responsible for the binding of these ligands over time, while the binding energy (ΔGbinding) values showed the energetic contribution of these residues to the stabilization of the APSrAB-ligand complex (mainly Arg265). Thus, compounds 13d, 14a, 14d, 16c, and 16d showed ΔGbinding values more favorable than -30.00 kcal mol-1 and had more affinity for the enzyme than the APS substrate, especially 16d, which can be pointed as an APSrAB potential inhibitor.