HOMOLOGY MODELING, ACTIVE SITE PREDICTION AND TARGETING THE ANTI EPILEPTIC ACTIVITY THROUGH MOLECULAR DOCKING TECHNIQUES ON LAFORIN

Abstract

Epilepsy is a second common neurological disorders characterized by repeated seizures. This is a genetic disorder caused by mutation in Laforin, encoded by the EPM2Agene. Laforin is a protein mutated in patients with Lafora disease. This contains a dual specificity phosphatase domain (DSP) and a carbohydrate binding module subtype 20 (CBM20). To develop antiepileptic drugs, understanding the characteristics of the protein responsible is essential. Hence EPM2A coding protein model has been built using Discovery Studio 3.5 and validated. The active site has been predicted for this model and analyzed.  Molecular docking studies have been performed for this model. To carry out docking studies  compounds having similar structure of Carbamazepen and the key amino acid residues involved in ligand binding have been determined from public databases. Totally 71 compounds has been screened and after conducting toxicity studies 5 compounds 2_4_-bis ( N_ - (4-methylphenyl) ureido) toluene, carboxyphenylureido phenyl, N- 3-( ( 2-methylphenyl )amino carbonyl amino)-2-naphthoyl, 1-Phenyl-3-(2-carboxy-phenyl)-urea and 2_6_- bis (N - ( 4 – methylphenyl ) ureido) toluene has been selected as potent target candidate drugs for Lafora disease.