An Insilico approach to design the mutated 3D structure of BCHE using AB initio method and testing the efficacy of the selected ligands in inhibiting the S226G mutation

Butyryl cholinesterase (BCHE) is a protein belonging to ester lipase super family. It hydrolyzes choline esters in addition to its role in nerve impulse transmission. BCHE has three active sites located at 226, 353 and 456 which are responsible for acyl ester intermediate, and charge relay system. Among the three sites, 226 (serine) have been reported to have the natural variant S 226 G. Alteration at this site affects the functionality of the protein due to its importance in the active site formation. Variations in this gene have also been reported in BCHE deficient conditions. BCHE is implicated to have a role in lipid metabolism; any alteration to its function causes a hindrance to the mobilization of fats leading to obesity which causes Type II Diabetes. Present work involves complete analysis of BCHE gene with reference to the site S226G and designing the mutated BCHE structure using AB Initio approach. Docking studies were performed with potent lead molecules with an aim to inhibit or minimize the adverse effect of the mutation.