Preprint Article Version 1 This version is not peer-reviewed

Identification of Potent Inhibitors against Aurora Kinase A Using Molecular Docking and Molecular Dynamics Simulation Studies

Version 1 : Received: 21 August 2019 / Approved: 23 August 2019 / Online: 23 August 2019 (05:01:40 CEST)

How to cite: Chinnasamy, S.; Selvaraj, G.; Chandra Kaushik, A.; Kaliamurthi, S.; Nangraj, A.S.; Selvaraj, C.; Singh, S.K.; Thirugnanasambandam, R.; Gu, K.; Wei, D. Identification of Potent Inhibitors against Aurora Kinase A Using Molecular Docking and Molecular Dynamics Simulation Studies. Preprints 2019, 2019080238 (doi: 10.20944/preprints201908.0238.v1). Chinnasamy, S.; Selvaraj, G.; Chandra Kaushik, A.; Kaliamurthi, S.; Nangraj, A.S.; Selvaraj, C.; Singh, S.K.; Thirugnanasambandam, R.; Gu, K.; Wei, D. Identification of Potent Inhibitors against Aurora Kinase A Using Molecular Docking and Molecular Dynamics Simulation Studies. Preprints 2019, 2019080238 (doi: 10.20944/preprints201908.0238.v1).

Abstract

Aurora kinase A (AURKA) is a normal cell proliferation-inducing enzyme encoded by AURKA gene, with over-expression observed in different types of malignancies. Hence, the goal is to find potential inhibitors against AURKA. In this study, molecular docking, Standard Precision and Extra Precision methods were employed. After the docking study, the ligands showed an extremely low binding score which suggested very high binding affinity of the ligands. Furthermore, Quantum polarized ligand docking (QPLD) was performed to predict the binding status of the molecules. Based on the binding affinity, the top four compounds were chosen for further analysis. The docked complexes were further analyzed in explicit water conditions using 100 ns molecular dynamics simulations and binding free energy calculation. Then, density functional theory (DFT) calculation was used to calculate the molecular properties of the molecules. Finally, systems biology experiments validated the molecular docking and molecular dynamics simulation studies and indicated that quercetin, kaempferol, luteolin and rutin could inhibit the AURKA. The results show that, these four molecules have high binding affinity to the AURKA and significant interactions (LEU139, GLU211and ALA213) were also identified with the hinge region of Aurora kinase A. Thus, LEU139, GLU211, and ALA213 were identified as the crucial protein mechanisms.

Subject Areas

aurora kinase A; molecular docking; DFT; MD simulation

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.