Protein Docking studies of target proteins using Metformin hydrochloride as a ligand

Abstract

Metformin hydrochloride is used as ligand to study its binding interactions with target proteins GLUT-1, GLUT -3, IR and Hexokinase through SWISSDOCK. Protein docking is performed using defined parameters of SWISSDOCK like high calculated affinity in each interaction and the drug showed fruitful interactions with the glycolytic enzyme HK and all the proteins like GLUT-1, GLUT-3 and IR that facilitate glucose uptake. GLUT- 1 interacts with metformin hydrochloride at ASn 98, Met 94, Ileu 196, Phe 137 and Trp386 positions where as metformin hydrochloride interacts with GLUT-3 transporter and shows protein ligand interactions at Phe 81 position, met77 and Ileu 78th positions through hydrogen bonds between carboxylate and ‘N’ of metformin. GLUT-3 transporter in glucose bound state shows interactions with ligand at ASn315 forming hydrogen bond with N of metformin and O of ASn carboxylate. Other possible interactions include Phe 414, Thr 411, Asn 409 (with O of Asn and N of metformin), Trp 410 and Gln 281positions. Metformin interacts with IR at ASP 1150, ASn 1137 (Hydrogen bonding b/n ‘O’ of carboxylate of ASn and N of the drug) and C, H &N of Tyr 1158 interacts with N of the drug. Metformin hydrochloride interacts with Hexokinase and Hexokinase bind to ATP analogue at positions like Glu 249 showing ionic interactions between N of drug metformin with C of Glutamic acid at 249 positions. Leu795 ‘O’ interacts with N of metformin by hydrogen bonding interactions. Ileu 245, Val 248 and Arg 243 by hydrogen bonding between N of drug and O of the amino acids Ileu 245, Val 248 and Arg 243 (Hexokinase + ATP analogue). Drug does not show Hydrophobic interactions and π- interactions with the proteins studied.