An integrated computational study for screening medicinal plant phytochemicals for possible inhibitors of the human bile salt exporter pump

Abstract

Background: The primary carrier of bile acids in humans is the bile salt export pump (BSEP). which are crucial for the digestion and absorption of fat. Type 2 progressive familial intrahepatic cholestasis (PFIC-2), which is brought on when BSEP is suppressed and causes a decrease in bile flow and a buildup of cytotoxic bile salts in the liver, is one of the main causes of cholestasis in Saudi Arabia. Elucidate the inhibitory potential with minimal or no adverse effects. Methods: The structure (6LR0) was downloaded from the PDB. Protein active sites were anticipated because these are pockets where ligands can bind and perform reactions to treat an infection. The PubChem zinc and mpd3 databases were used to get the ligands' structures. Molecular operating environment (MOE) was utilized to perform molecular docking of 1600 phytochemicals against BSEP. LigX was used to observe the docking hits for interaction analysis. Results: identification of 4 potential candidates for binding to the BSEP active site. then, Protox II-was used to forecast toxicity for the selected hits. Molecular dynamics simulations were also used to assess the binding complex's stability in water for 100 nanoseconds. The strong binding affinity of high-ranked drugs was predicted by our molecular docking and simulation. Conclusions: This approach could be useful in determining the efficiency of a therapeutic molecule in the therapy of the BSEP. The aim of this research is to identify novel -BSEP drug targets, and in future in vitro and in vivo research could prove its clinical efficiency.