An Integrated Computational Study for Screening Medicinal Plant Phytochemicals for Possible Inhibitors of the Human Bile Salt Exporter Pump

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Dhafer B. Alshehri

Abstract

Background: In humans, the bile salt export pump (BSEP) is the main transporter of bile acids from hepatocytes into bile.  This increases dietary fat digestion and absorption by facilitating the production of micelles. One of the major causes of cholestasis in Saudi Arabia is type 2 Progressive Familial Intrahepatic Cholestasis (PFIC-2), which is caused when BSEP is inhibited and results in decreased bile flow and an accumulation of cytotoxic bile salts in the liver.


Objectives: An attempt was made in this work to 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: This research identified four potential candidates for binding to the BSEP active site. After that, 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. This approach could be useful in determining the efficiency of a therapeutic molecule in the therapy of the bile salt exporter pump. 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.


Conclusions: This approach could be useful in determining the efficiency of a therapeutic molecule in the therapy of the bile salt exporter pump. 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

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