Docking Study to Predict the Efficacy of Phosphatidylinositol 3-Kinase α Inhibitors

Mahmoud A. Chawsheen; Hazem A. Al-Bustany

doi:10.14500/aro.10565

Mahmoud A. Chawsheen Department of General Sciences, Faculty of Education, Soran University, Erbil, Kurdistan Region http://orcid.org/0000-0003-2277-1984
Hazem A. Al-Bustany Department of Basic Science, College of Medicine, Hawler Medical University, Erbil, Kurdistan Region http://orcid.org/0000-0003-2934-8505

Keywords: AutoDock Vina, Cancer cell, Cell signaling, Docking, Phosphatidylinositol 3-kinase, Phosphatidylinositol 3-kinase α

Abstract

The phosphatidylinositol 3-kinase (PI3K) family comprises lipid kinases that cross-link signals between living cells and their surroundings. PI3Ks are classified into several groups and isoforms with specific characteristics and functions. Genes encoding PI3Ks are mutated in several types of cancer, and their isoforms have varying capacity in promoting cell signaling and cancer progression. Many compounds have been introduced as PI3Kα inhibitors, but not all of them have the same inhibitory effects. For successful PI3K-related biomedical experiments, it is vital to select the most specific and potent compounds with the highest inhibitory effects for targeting this kinase. In this study, we investigate 28 well-recognized PI3Kα inhibitors through predicting their specificity and potency using the docking software AutoDock Vina. Our data showed that PF 05212384 had the highest docking score (−9.2 kcal/mol), and 3-methyladenine had the lowest docking score (−4.8 kcal/mol). Our data also showed different types of interactions and bonds formed between the inhibitors and protein residues. In conclusion, PF 05212384 and AZD 6482 compounds are the best candidates for targeting PI3Kα. In addition to hydrophobic interactions in the PI3Kα binding pocket, the formation of hydrogen bonds between these inhibitors and binding pocket residues was confirmed.

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Author Biographies

Mahmoud A. Chawsheen, Department of General Sciences, Faculty of Education, Soran University, Erbil, Kurdistan Region

Mahmoud Ahmed Chawsheen is Assistant Professor at the Department of General Sciences, Faculty of Education, Soran University. He got the B.Sc. degree in Biological Sciences, the M.Sc. degree in Cell Biology and the Ph.D. degree in Cell Biology. His research interests are in cell signalling, cell death and migration in cancer, multi-drug resistant, and docking studies. Dr. Mahmoud is a member of European Association for Cancer Research, and Royal Microscopical Society.

Hazem A. Al-Bustany, Department of Basic Science, College of Medicine, Hawler Medical University, Erbil, Kurdistan Region

Hazem Abbas Al-Bustant is a Researcher, Senior Biologist at the Department of Basic Science, College of Medicine, Hawler Medical University. He got the B.Sc. degree in Biology, the M.Sc. degree in Molecular Biology. His research interests are in Molecular Docking, Computational Drug Design and Cancers. Al-Bustany is a member of Kurdistan Biology Syndicate.

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