Applications of 3D-QSAR and structure-based pharmacophore modeling, virtual screening, ADMET, and molecular docking of putative MAPKAP-K2 (MK2) inhibitors

Abstract

MAPKAP-K2 (MK2) belongs to the Ser/Thr kinase family, and has emerged as a highly favored target in the search for efficacious and safe anti-inflammatory drug. Thus, 3D-QSAR and structure-based pharmacophore models were developed in this study to identify new potential leads inhibiting MK2 as an efficient way to treat rheumatoid arthritis. Furthermore, these two kinds of models were cascaded together to reduce false positives in virtual screening. The selected compounds were further analyzed and refined using drug-like filters and ADMET analysis. Subsequently, 105 recruited hits were docked into MK2-binding site with GOLD. Finally, 12 molecules were selected as potential MK2 inhibitors, and their consensus score and their structural diversity were evaluated.