3D-QSAR, molecular docking and dynamics simulation of difluorophenol pyridine derivatives as RSK2 inhibitor
Muhammad Arba, Hamzah Azali, Sabarudin Ombe, Alrum Armid, Ida Usman · Journal of Applied Pharmaceutical Science · 2019
Given the increasing role of P90 Ribosomal S6 Kinase 2 (RSK2) as an anticancer drug target, we performed 3D-Quantitative structure-activity relationship, including comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) on difluorophenol pyridine derivatives as the inhibitor of RSK2.CoMFA model with q 2 of 0.597 and R 2 of 0.993, while CoMSIA model with q 2 of 0.563 and R 2 of 0.993, were obtained.The predictive ability of both models was assured using a test set compound with R 2 pred values of 0.996 each.Using the validated models, novel compound was proposed and its interaction with RSK2 was investigated employing molecular docking and molecular dynamics simulation of 50 ns.Furthermore, molecular-mechanics Poisson-Boltzmann surface area calculation was performed.The result showed that the newly designed compound has a comparable binding free energy with the known RSK2 inhibitor, indicating its potential as a new RSK2 inhibitor.