Virtual screening of potential inhibitor against breast cancer-causing estrogen receptor alpha (ERα): molecular docking and dynamic simulations

Breast cancer (Bc a ) causes the highest rate of mortality in females owing to the out-of-control cell division in breast cells. In this work, we perform an in-silico screening based on molecular docking and molecular dynamic of curcumin derivatives against ERα. In this study, we carry out, molecula...

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Bibliographic Details
Published in:Molecular simulation 2022-09, Vol.48 (13), p.1163-1174
Main Authors: Muhammad, Shabbir, Saba, Afsheen, Khera, Rasheed Ahmad, Al-Sehemi, Abdullah. G., Algarni, H., Iqbal, Javed, Alshahrani, Mohammad Y., Chaudhry, Aijaz Rasool
Format: Article
Language:English
Subjects:
Binding energy
Biocompatibility
Breast cancer
Cell division
Curcumin derivatives
Estrogens
Free energy
Inhibitors
Ligands
MM-PBSA
Molecular docking
Molecular dynamics
Toxicity
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Summary:Breast cancer (Bc a ) causes the highest rate of mortality in females owing to the out-of-control cell division in breast cells. In this work, we perform an in-silico screening based on molecular docking and molecular dynamic of curcumin derivatives against ERα. In this study, we carry out, molecular docking of fifty (50) curcumin derivatives having anticancer potential by using virtual screening tools. Ten (10) ligands were selected based on binding energy ranged from (-7.4 kcal/mol to -9 kcal/mol), lower values of inhibition constant (0.23µmol to 3.59µmol), and visualisation of intermolecular interactions. Additionally, we also assess ADMET properties of selected ligands for prediction of their toxicity and drug-likeness. The molecular dynamic simulations (MD) including RMSD, RMSF, Rg, SASA, number of H-bonds and MM-PBSA binding free energy results showed that ligand L2 and L8 bind to estrogen protein ERα more proficiently with good stability over 120 ns. These results suggest lead anticancer compounds L2 (Salicylidenecurcumin) and L8 (Curcumin difluorinated) are the most promising inhibitor against ERα of Bc a with ∆G bind values of (-2.939 and -4.369) kcal/mol. we expect that our findings will evoke the scientific community to further do in-vitro and in-vivo investigations for screened curcumin derivatives against ERα of Bc a.
ISSN:0892-7022
1029-0435
DOI:10.1080/08927022.2022.2072840