Structural Characterization of Alpha-methylacyl-CoA Racemase: Comparative Structural Modeling, Molecular Docking and Dynamic Simulations Studies

α-Methylacyl-CoA racemase (AMACR) has recently been reported as a vital solid tumor marker and is an attractive target for designing anti-tumor agents. It is a mitochondrial and peroxisomal enzyme which plays a central role in the oxidation of cholesterol metabolites and branched chain fatty acids. The three dimensional structure of human AMACR is still unknown. In the current study, homology model using Modeller and different modelling servers based on 1X74A as template is reported. The three dimensional model generated was validated and evaluated using various available programs like PROCHECK, ERRAT, ProSA energy plots, etc. In order to find potent inhibitors of AMACR, a docking study using compounds reported to be active against this enzyme of other organisms was conducted. Among the studied inhibitors, 2-methylmyristoyl- CoA effectively binds to and inhibits the enzyme by means of hydrogen bond interactions with the key residues of pocket. Moreover, molecular dynamics simulation was carried out to check the stability of AMACR/2-methylmyristoyl-CoA complex. The results illustrated the ligand’s high binding affinity with enzyme and the stability of hydrogen bond interactions in dynamic condition. Hence, 2-methylmyristoyl-CoA has been suggested to be a promising lead compound for the design of new inhibitors against AMACR.