Ferdowsi University of Mashhad

Document Type : Research Articles


1 ferdowsi university of mashhad, Iran. Department of Biology, Kavian Institute of Higher education, Mashhad, Iran School of Science and Technology, The University of Georgia, Tbilisi, Georgia

2 Department of Biology. Kavian Institute of Higher Education

3 Department Of psychology, Sheffield Hallam university, Sheffield, United Kingdom

4 Department of Biology, Kavian Institute of Higher Education, Mashhad, Iran

5 College of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran



Cytochromes are enzymes of the dehydrogenase class with a hemoprotein structure in which the iron in these compounds undergoes oxidation and reduction reactions upon receiving or losing electrons. Quantitatively speaking, CYP3A4 is the most important isoenzyme of cytochrome P450, oxidizing foreign organic molecules such as drugs or toxins to cause them to leave the body. Many drugs and antibiotics can induce or inhibit the activity of cytochrome P450, including dexamethasone. Dexamethasone is a steroidal anti-inflammatory drug used in the treatment of inflammatory diseases and chronic autoimmunity. This study aimed to investigate the induction effect of dexamethasone and its inhibition of biotransformation pathways by in silico methods. Melegro virtual docker software was used to investigate the molecular docking of the enzyme and dexamethasone, which indicated the proper binding of the drug to the enzyme. The molecular simulation was performed in Linux with the Gromacs program, and RMSD and gyrus radius were evaluated. The results were analyzed with Pymol and VMD software, and the obtained curve was plotted with GRACE software. Docking results show that a cluster with a bond energy of -60.81 was the best cluster and the bond size between ligand and internal atoms was -23.191in the complex. In addition, the amount of bond between the ligand and water for this pose was zero. The stability of the enzyme-drug complex and the induction effect of dexamethasone on CYP3A4 were indicated by RMSD and the radius of gyration results. Results of RMSD and the radius of gyration of cytochrome P450 glucocorticoid obtained from the simulation showed the stability of binding of the drug to the enzyme. Also, RMSD results showed the stability of glucocorticoid and dexamethasone complex during molecular dynamics simulation. It reached relative stability at 0.8 nm after 80,000 ps until the end of the simulation.