Pharmacophore Modeling and Molecular Dynamics Simulation to Find the Potent Leads for Aurora Kinase B

摘要

Identification of the selective chemical features for Aurora-B inhibitors gained much attraction in drug discovery for the treatment of cancer. Hence to identify the Aurora-B critical features various techniques were utilized such as pharmacophore generation, virtual screening, homology modeling, molecular dynamics, and docking. Top ten hypotheses were generated for Aurora-B and Aurora-A. Among ten hypotheses, HypoB 1 and HypoAl were selected as a best hypothesis for Aurora-B and Aurora-A based on cluster analysis and ranking score, respectively. Test set result revealed that ring aromatic (RA) group in HypoB 1 plays an essential role in differentiates Aurora-B from Aurora-A inhibitors. Hence, HypoB 1 used as 3D query in virtual screening of databases and the hits were sorted out by applying drug-like properties and molecular docking. The molecular docking result revealed that 15 hits have shown strong hydrogen bond interactions with Alal57, Glul55, and Lys 106. Hence, we proposed that HypoB 1 might be a reasonable hypothesis to retrieve the structurally diverse and selective leads from various databases to inhibit Aurora-B.