3D-QSAR, molecular docking and dynamics simulation of difluorophenol pyridine derivatives as RSK2 inhibitor
Loading...
Date
2019-06
Journal Title
Journal ISSN
Volume Title
Publisher
Open Science Publishers LLP
Abstract
Given the increasing role of P90 Ribosomal S6 Kinase 2 (RSK2) as an anticancer drug target, we performed3D-Quantitative structure–activity relationship, including comparative molecular field analysis (CoMFA) andcomparative molecular similarity indices analysis (CoMSIA) on difluorophenol pyridine derivatives as the inhibitorof RSK2. CoMFA model with q2 of 0.597 and R2 of 0.993, while CoMSIA model with q2 of 0.563 and R2 of 0.993,were obtained. The predictive ability of both models was assured using a test set compound with R2pred values of 0.996each. Using the validated models, novel compound was proposed and its interaction with RSK2 was investigatedemploying molecular docking and molecular dynamics simulation of 50 ns. Furthermore, molecular-mechanicsPoisson–Boltzmann surface area calculation was performed. The result showed that the newly designed compoundhas a comparable binding free energy with the known RSK2 inhibitor, indicating its potential as a new RSK2 inhibitor.
Description
Keywords
3D-QSAR, CoMFA, CoMSIA, docking, difluorophenol pyridine.
Citation
Arba Muhammad, Hamzah Azali, Ombe Sabarudin, Armid Alrum, Ida Usman. 3D-QSAR, molecular docking and dynamics simulation of difluorophenol pyridine derivatives as RSK2 inhibitor. Journal of Applied Pharmaceutical Science. 2019 Jun; 2019 Jun: 001-009