Homology Modelling and Docking Studies of p85-alpha a subunit of Phosphatidylinositol 3-kinase with Anti-diabetic Compounds

The p85α regulatory subunit of phosphoinositide 3-kinase (PI3K), a key mediator of Insulin’s metabolic actions. This gene plays a major role in the mediation of insulin- stimulated glucose disposal. The understanding of this enzyme might significantly increase the knowledge on the design of novel anti-diabetic compounds. Thus in the present study, the 3D structure of PI3K-p85alpha was modelled by using Modeller9v9 and the structure was validated by checking its stereo chemical parameters through PROCHECK, Verfiy3D, and ERRAT at SAVES server. Further, the docking studies with the ten widely used anti-diabetic compounds were carried out by using FlexX suite. The docking interactions revealed that the Phenformin (CID-8249) is having strong interaction of -24.1844 kJ/mol and the lowest interaction of -13.9702 kJ/mol was observed for Saxagliptin. The docking interactions determined that Phenylalanine (Phe59) and Serine (Ser60) amino acids are crucial for H bond interactions and the Hydrophobic interactions (Non bonded) is flavoured by Tyrosine (Tyr 83) residues in the active site of PI3K alpha. The finding of this work might enhance the understanding of PI3K alpha resistance and also helps in design of novel anti-diabetic compounds.