IN SILICO DOCKING OF AMINOPYRIMIDINES TARGETING RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS (RAGE)

Vimalavathini R.*, Thamizharasi S., Vishvaja S., Srinithi S. and Yuvaraj G.

ABSTRACT

RAGE is a multi-ligand trans membrane receptor belonging to immunoglobulin superfamily involved in various physiological and pathological pathways of various diseases like cardio vascular diseases, cancer, neurodegenerative and auto immune diseases. Nearly 10 drugs of aminopyrimidine group (flucytosine, pyrimethamine, sulfadiazine, cytarabine, cidofovir, zalcitabine, lamivudine, capectitabine, sulfadimethoxine and sulfadimidine) were imported from PubChem database. The amino acids serine, histidine were predicted as active sites for RAGE receptor (PDB ID: 3CJJ) and the amino acids asparagine, lysine, glutamic acid, tryptophan, arginine, and tyrosine were predicted as active sites for RAGE receptor (PDB ID: 3O3U) using PDBSum database. The molecular docking were performed with RAGE receptor (PDB ID: 3CJJ and PDB ID: 3O3U) both with and without the selection of active sites, as rigid and flexible docking respectively. The docking studies were done using Autodock Tools 4.2 (Version 1.5.6rc3) software. The drugs sulfadimethoxine, sulfadimidine, capectitabine and pyrimethamine showed good docking profiles for PDB ID: 3CJJ whereas sulfadimidine, pyrimethamine, sulfadiazine and sulfadimethoxine showed good docking profiles for PDB ID: 3O3U. Finally the result from the study demonstrates the above mentioned drugs can be presumed as inhibitors of RAGE.

Keywords: RAGE, aminopyrimidine, PubChem, PDBSum, molecular docking, AutoDock.