Identification of potential Aurora kinase-C protein inhibitors: an amalgamation of energy minimization, virtual screening, prime MMGBSA and AutoDock

Abstract

Genomic instability is a trademark of cancer evolution, there is still a wide necessity to discover safe and effective anti-cancer drugs. Aurora kinase-C protein is a member of the Aurora kinase family involved in regulating mitosis phases of the cell cycle. Aurora kinase-C protein has an aberrant expression at spindle assembly checkpoint leading to human cervical cancer and colorectal cancer. Knowledge of 3D structure of the protein is vital for identify possible inhibitors. In the present study, 3D structure prediction of Aurora kinase-C protein is taken up by using comparative homology modeling techniques and minimized by NAMD-VMD Software. The quality of modeled protein was validated using ProSA and Ramachandran plot. Probable binding site in protein was identified from SiteMap and molecular docking based virtual screening was carried out using Asinex database to identify lead molecules. The obtained lead molecules were further optimized using PrimeMM-GBSA and AutoDock. ADME properties of the leads were calculated to ascertain the drug-like properties at lead molecules.Communicated by Ramaswamy H. Sarma.

Keywords: AutoDock; Cervical cancer and colorectal cancer; NAMD-VMD; Prime MM-GBSA; Schrodinger suite.