Prediction of dual agents as an activator of mutant p53 and inhibitor of Hsp90 by docking, molecular dynamic simulation and virtual screening
The new ligand was confirmed as a dual agent by molecular docking study and molecular dynamic simulations. Results were evaluated by molecular dynamic simulations on an Hsp90 pyrazole inhibitor and a p53 pyrazole activator that those activities had been confirmed through experimental research. A virtual screening was performed on ZINC database and a set of new dual agents has been proposed. These compounds show that substitution of pyrrole ring or any other group at position 3 of pyrazole ring is not necessary for the key interactions in two proteins. Phenyl segment at position 4 or 5 of pyrazole ring is important for hydrophobic interactions in both of them.
hsp90 heat shock protein90 mds molecular dynamic simulations rg radius of gyration rmsd root mean square deviation rmsf root mean square fluctuation vs virtual screening