Molecular dynamics guided insights for the inhibition of hydrolase. An approach towards rational design of inhibitors for lung cancer

SUMMARY. In the present research work, a series of novel analogues of crizotinib were designed in antici-pation for their inhibitory potential against lung cancer. In continuation to this study, two analogues namely CF-4 and CF-12 were chosen for molecular dynamic simulation. The selection criteria was based on their respective docking scores against the target MutT homolog (MTH1) a hydrolase class of target with PDB code 4C9W reported in our previous publications. Results of MD simulations suggested significant RMSD value of 4C9W backbone for CF-4 and CF-12 found to be 1.75 and 2.4 Å, respectively. Fur-ther, analysis of Protein-ligand 3D interaction diagrams of CF-4 and CF-12 complexes revealed that all the noteworthy interaction detected by IFD-XP docking pose were also detected during MD analysis. The insights from these findings could be used for further lead optimization to develop the potential hydrolase inhibitors against lung cancer.