Molecular Docking Studies of Vitamin K Epoxide Reductase Subunit۱

Vitamin K Epoxide Reductase (VKOR) is a membrane protein that regenerates Vitamin K ۲,۳-epoxide andconverts vitamin K to vitamin K hydroquinone by enzymatic catalysis. Considering the importance ofVKORC۱ protein in several diseases and its importance as the target of many protein complex inhibitoryantagonists in the prevention and treatment of thromboembolic diseases, cardiovascular diseases andmyocardial infarction, docking studies and evaluation of the binding and efficacy of existing drugs affectingthis protein are of particular importance. Common drugs for this protein include Warfarin, Brodifacoum,Phenindione, and Cholorophacinone. It seems that docking and the study of protein-ligand binding onVKORC۱ protein with the aim of evaluating available drugs in the market, can have a significant impact onthe promotion of drug discovery studies. For this purpose docking of VKORC۱ with each drug done byAutoDock software. By comparing the energy of the best conformation from each cluster for variousVKORC۱ protein antagonists and Vitamin K Epoxide, it was found that the best drugs in inhibiting thisreceptor and subsequently preventing related diseases, are Brodifacoum, Chlorophacinone, Warfarin andPhenindione, respectively. Also, all of these drugs bind with more binding energy than the main proteinligand (Vitamin K Epoxide), which indicates the effectiveness of all these drugs. This could be due to anincrease in the number of amino acids involved in binding at the active site of the enzyme based oninformation from comparisons in Ligplus software.

Keywords:

Molecular Docking , VKORC۱ , AutoDock , Brodifacoum , Chlorophacinone