Computational Simulations to Predict the Inhibitor Against Organic Anion Transporters 1 To Modulate Drug Concentration in Blood

Organic anion transporters (OAT1) are proteins that are located in the kidney and are responsible for excretion of metabolic byproducts, toxins, and drugs from the blood. Inhibiting these transporters can help in regulating the drug concentrations in the bloodstream. Recently, two separate studies have elucidated the 3D structure of OAT1 using cryogenic electron microscopy. These structures will be helpful in understanding the OAT1 drug binding and releasing mechanism. This in turn will help in designing drugs that can control the OAT1 functioning and help in controlling the drug concentration in blood. We hypothesize that the OAT1 should have a specific drug binding site where the drug can bind and cease or slower its functioning. In the current work, we have utilized molecular docking simulations to predict the inhibitors that can bind to the OAT1 substrate binding site. Ligand binding to this site will competitively inhibit the substrate, thereby inhibiting OAT1 function. A total of 5000 chemical compounds (ligands) were downloaded from the Zinc20 database for docking simulations. Based on the docking score, top five ligands were selected for further analysis. These ligands formed strong interactions with the protein, as analyzed using the PLIP web server. In addition, the ligand showed drug likeliness properties, a measure of their potential as drugs. Further analysis is required to investigate the dynamics and organic anion transport mechanism of this protein. In summary, computational tools were used to predict the OAT1 protein, offering potential for modulating drug concentrations in blood.