Dasatinib–SIK2 Binding Elucidated by Homology Modeling, Molecular Docking, and Dynamics Simulations
Mingsong Shi, Lun Wang, Penghui Li, Jiang Liu, Lijuan Chen, Dingguo Xu
Abstract
-(2-chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide (dasatinib), and constructed four representative SIK2 structures by homology modeling. We investigated the interactions between dasatinib and SIK2 via molecular docking, molecular dynamics simulation, and binding free energy calculation and found that dasatinib showed strong binding affinity for SIK2. Binding free energy calculations suggested that the modification of various dasatinib regions may provide useful information for drug design and to guide the discovery of novel dasatinib-based SIK2 inhibitors.
Topics & Concepts
DasatinibHomology modelingDocking (animal)ChemistryMolecular dynamicsVirtual screeningKinaseRational designCalmodulinComputational biologyStereochemistrySignal transductionEnzymeBiochemistryBiologyMedicineComputational chemistryTyrosine kinaseGeneticsNursingProtein Kinase Regulation and GTPase SignalingChronic Myeloid Leukemia TreatmentsQuinazolinone synthesis and applications