Molecular Modelling of Cytochrome P450 2A5 [Mus musculus] and Molecular Docking Studies Involved in Non-Alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the world's population and is the principal cause of cirrhosis and hepatocellular carcinoma. NAFLD is a disease spectrum that includes steatosis with or without moderate inflammation (non-alcoholic fatty liver) and non-alcoholic steatohepatitis (NASH), which is characterised by necroinflammation and a faster fibrosis progression than NAFLD. The pathophysiology of various liver illnesses also involves the hepatic CYPs. By controlling lipid metabolism-related pathways, such as oxidative stress, arachidonic acid metabolism, steroid hormone metabolism, and fatty acid metabolism, the CYP450 family plays an important role in the pathophysiology of fatty liver. Hepatotoxicity is brought on by medicines that are activated by CYP to produce harmful metabolites. Drugs, substances, and endogenous substrates are all metabolized by cytochrome P-450 (CYPs). Since the enzyme's crystal structure has not yet been made public, we created a homology model of Cytochrome P450 2A5 using a modeller. The optimized homology model was evaluated as a trustworthy structure by PROCHECK, ERRAT, WHAT-IF, PROSA2003, and VERIFY-3D after molecular dynamic refinement. NASH pathogenesis is complex, with multiple hits such as oxidative stress, free fatty acid-induced lipotoxicity, endoplasmic reticulum stress, cytokines, and gut flora all contributing to steatosis, liver injury, and disease progression (the integrated response hypothesis). Because these pathways contribute to the insulin resistance phenotype of NAFLD, treatments that improve it, such as thiazolidinediones (TZDs), may be beneficial. Hence Furan thiazolidinedione’s physical and chemical properties are studied and protein Cytochrome P-450 2A5 is docked with Furan thiazolidinedione using docking tools.