Computational Screening of Potential Inhibitors of Desulfobacter postgatei for Pyrite Scale Prevention in Oil and Gas Wells

Sulfate-reducing bacteria (SRB) such as Desulfobacter postgatei are often found in oil and gas wells. However, they lead to the release of hydrogen sulfide which in turn leads to the formation of iron sulfide scale such as pyrite. ATP sulfurylase is an enzyme present in SRB, which catalyzes the formation of adenylyl sulfate (APS) and inorganic pyrophosphatase (PPi) from ATP and sulfate which is one of the first steps in hydrogen sulfide production by D. postgatei. Virtual screening using molecular docking and machine learning tools was used to identify three potential inhibitors of ATP sulfurylase from a database of about 40 million compounds. These selected hits ((S,E)-1-(4-methoxyphenyl)-3-(9-((m-tolylimino)methyl)-9,10-dihydroanthracen-9-yl)pyrrolidine-2,5-dione;,methyl 2-[[(1S)-5-cyano-2-imino-1-(4-phenylthiazol-2-yl)-3-azaspiro[5.5]undec-4-en-4-yl]sulfanyl]acetate and (4S)-4-(3-chloro-4-hydroxy-phenyl)-1-(6-hydroxypyridazin-3-yl)-3-methyl-4,5-dihydropyrazolo[3,4-b]pyridin-6-ol), which are known as A, B and C respectively) all had good binding affinities with ATP sulfurylase and were further analyzed for their toxicological properties. The molecular docking results showed that all the compounds have negative binding energy with compound A having the highest docking score. However, based on the physicochemical and toxicological properties, compound C is the best choice as it does not violate any of the recommended properties that relate to absorption and distribution. Only compound C was predicted to be both safe and effective as a potential inhibitor of ATP sulfurylase. The binding mode of compound C revealed favorable interactions with the amino residues LEU 213, ASP 308, ARG 307, TRP 347, LEU 224, GLN 212, MET211 and HIS 309.