Identification of 2,4-diarylaminopyrimidine analogues as ALK inhibitors by using 3D-QSAR, molecular docking, and molecular dynamics simulations

摘要: Anaplastic lymphoma kinase (ALK) is a particularly promising target for the development of small molecule anti-cancer drugs. In present study, comparative molecular field analysis (CoMFA) and similarity indices (CoMSIA) were performed on 60 ALK inhibitors to build three-dimensional quantitative structure–activity relationship models. Both ligand-based resultants CoMFA (r 2 0.970, q 0.660) CoMSIA 0.979, 0.623) models exhibited good predictability. The resulting contour maps illustrated regions where interactive fields may affect activity. Molecular docking was then explore interactions between these ALK-4DCE protein. A few key residues (His32, Gly31, Gly169, Asp170, Val35, Ala100, Pro160, Lys50, Leu30) at binding site 4DCE identified. dynamics simulation further verified reliability. information acquired in this work not only provides better appreciation molecules receptor but could also be applied design more effective inhibitors.