TY - JOUR
T1 - Molecular dynamics guided insights for the inhibition of hydrolase. An approach towards rational design of inhibitors for lung cancer
AU - Kamath, Venkatesh
AU - Khatun, Babli
AU - Pai, Aravinda
N1 - Funding Information:
Authors ackknowledge Manipal Academy of Higher Education for the reserch support.
Publisher Copyright:
© 2020, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
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M3 - Article
AN - SCOPUS:85097313039
SN - 0326-2383
VL - 39
SP - 2498
EP - 2501
JO - Latin American Journal of Pharmacy
JF - Latin American Journal of Pharmacy
IS - 12
ER -
