• A comparative study of the effects of Atorvastatin, Simvastatin, Atorvastatin and Lovastatin on SLCO1B1, using molecular docking methods.
  • Bahar Akbari,1,*
    1. IAU, medical sciences, Tehran branch


  • Introduction: Drug discovery and molecular docking is a challenging process, and identifying the right lead compound is a determining factor in the overall success of the project. This paper discusses the process of drug discovery and molecular docking, which is a challenging process. The paper focuses on identifying the right lead compound, which is a determining factor in the overall success of drug discovery. The study compares the effects of Atorvastatin, Simvastatin, and Lovastatin on SLCO1B1 using molecular docking methods. SLCO1B1 is a protein found in humans that belongs to the solute carrier organic anion transporter family. It transports various types of organic anions, conjugated steroids, eicosanoids, and thyroid hormones. The wide range of compounds transported by SLCO1B1 suggests it plays an important role in the clearance of endogenous and exogenous substances from the liver and other tissues. The pH sensitivity of SLCO1B1 towards certain compounds suggests that the binding site of the protein may be affected by the acidity of the surrounding environment, which could have implications for its function in different tissues. Atorvastatin (ATV) is a medication used to lower cholesterol and lipid levels in the blood, reducing the risk of cardiovascular disease. It belongs to the statin class of medications and works by inhibiting the endogenous production of cholesterol in the liver. Statins are the most commonly prescribed medication for treating abnormal lipid levels. ATV is transported in the blood almost exclusively bound to plasma proteins and is subject to pre-systemic clearance at the gastrointestinal tract and to first-pass hepatic clearance, which explains its low systemic bioavailability. Elimination of ATV and its metabolites is principally biliary, with no significant enterohepatic recirculation. Simvastatin is a medication derived from Aspergillus terreus and is used to lower the risk of cardiovascular disease by inhibiting cholesterol production. It belongs to the statin class of medications, which inhibits the enzyme HMG-CoA Reductase involved in producing of cholesterol and other lipid compounds. Statins, including simvastatin, atorvastatin, and lovastatin, are widely prescribed due to their proven benefits and minimal side effects. Elevated cholesterol levels, especially LDL levels, are a significant risk factor for CVD, and statins have been shown to effectively reduce this risk. Statins are cost-effective and beneficial even for low-risk individuals, as they can significantly reduce the occurrence of major cardiovascular events without significant side effects. Lovastatin is a medication derived from a fermentation product of Aspergillus terreus and belongs to the statin class of medications. It is used to lower the risk of cardiovascular disease by inhibiting the production of cholesterol in the liver. Statins, including lovastatin, competitively inhibit the enzyme HMG-CoA Reductase, which is involved in producing cholesterol and other lipid compounds. Statins are widely prescribed due to their proven benefits and minimal side effects. Elevated cholesterol levels, especially low-density lipoprotein (LDL) levels, are a significant risk factor for CVD. Statins have been proven to effectively lower LDL levels and reduce the risk of CVD and all-cause mortality, even in low-risk individuals. Rosuvastatin is the most potent statin medication, while lovastatin has a lower average decrease; however, clinical outcomes between statins show minimal differences.
  • Methods: For the preparation of the macromolecule, we use websites such as Uniprot to extract the 3d structure of our protein. The most suitable protein structure is one with a high resolution, less chains and a higher amount of nucleotides. The best format for saving the protein is PDB After finding the 3d structure, we open the protein in UCSF Chimera, for the purposes of deleting the unwanted chains, side-chains, etc. Then we will prepare it for docking by going to the tools menu and clicking Surface/Binding Analysis - Dock Prep. We have used chain A of the protein SLCO1B1. For the preparation of the ligand- drug-, we first download the suitable drugs using websites such as PubChem. Then we will download the ligands 3d structure with the SDF format. We usd the drugs Lovastatin, Simvastatin and Atorvastatin. Both the ligand and the receptor are opened in PyRx. PyRx is a Virtual Screening software for Computational Drug Discovery that can be used to screen libraries of compounds against potential drug targets. First, the ligands and the receptor are opened in PyRx. Then we will select the perfect site action for the ligands. After this selection, the software will start docking.
  • Results: The results will be shown below the screen after the docking is done. In the case of the binding affinity, the more negative the numbers, the better the result. RMSD lower and upper bonds should also be zero, for a good result. Binding affinities of atorvastatin, simvastatin and lovastatin are as follows: -8.4, -7.9, -7.6
  • Conclusion: Among the mentioned drugs, atorvastatin is the most effective for SLCO1B1 protein malfunction illnesses.
  • Keywords: SLCO1B1, Molecular docking, Atorvastatin, Simvastatin , Lovastatin