Structural Analysis of the Inhibition of Cdk4 and Cdk6 by p16INK4athrough Molecular Dynamics Simulations

摘要: Cyclin-dependent kinases 4, 6 and 2 (Cdk4/6/2), are proteins that lead progression through the G1-S transition, a step strictly regulated in process of cell proliferation. The p16(INK4a) tumor suppressor, whose expression is inhibited high number cancers, binds to Cdk4/6 inhibits phosphorylation retinoblastoma protein, forcing cells remain G1 phase therefore, arresting division. Accordingly, design small compounds mimicking inhibition appears be promising way treat cancer. In order get some insight into key interactions governing recognition between different cyclin-dependent present work reports results molecular dynamics simulations both, Cdk6-p16(INK4a) complex Cdk4-p16(INK4a) complex, respectively at 300 K. Most observed, were already anticipated analysis crystal structure Cdk6-p16(INK4a). However, few features found out from these calculations provide better understanding role T-loop conformation, fragment Cdks, ATP binding-site distorted upon binding p16(INK4a).