ALLOSTERIC MODULATION OF AURKA KINASE ACTIVITY BY ARKIN-A VIA DYNAMIC CORRELATION NETWORK ANALYSIS

Protein phosphorylation and post-translational modification by protein kinases are crucial cell signaling and regulatorysystems. AurkA, a serine/threonine kinase, controls mitotic cell division and has sequence homology with other kinases.Clinical trials are underway to target AurkA Kinase’s overexpression in human cancer using ATP-competitive drugs.AurkinA, a small allosteric inhibitor, binds to TPX2’s Y-pocket, which holds Y8 and Y10. AurkinA drug-likeinhibitors delocalize the kinase from cell spindle formation, disrupting the Aurka–Tpx2 complex. The allostericmechanism for these compounds is unclear at the molecular level. To understand the allosteric mechanism, all-atommolecular dynamics simulations were employed to create fluctuation association networks. The fluctuation correlationnetworks of AurkA-Tpx2 and AurkinA vary significantly. AurkA-AurkinA transfers information from theallosteric to the catalytic sites more readily than AurkA-Tpx2. These methods will help develop route-targeted drugsand create protein allosteric circuits.Study Design: Molecular dynamics simulations, an investigative strategy, and AurkA kinase allostery.Duration And Place Of Study: Department of Health, Medical Teaching Institution Mardan Medical ComplexMardan, form jan 2018 to jan 2019Keywords: AurkA kinase, TPX2, AurkinA, MD simulation