scholarly journals Molecular Dynamics Simulation Estrogen Receptor Alpha againts Andrographolide as Anti Breast Cancer

2019 ◽  
Vol 6 (2) ◽  
pp. 65
Author(s):  
Doni Dermawan ◽  
Riyadi Sumirtanurdin ◽  
Deti Dewantisari
Keyword(s):  
Breast Cancer ◽  
Molecular Dynamics ◽  
Estrogen Receptor ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Estrogen Receptor Alpha ◽  
Docking Simulation ◽  
Dynamics Simulation ◽  
Receptor Alpha ◽  
A Value

Breast cancer is the most common cancer suffered by women with 1.67 million new cases in the world by 2012 with a mortality rate of 12.9%. Tamoxifen is a standard therapy for breast cancer but can cause endometrial and thromboembolic cancer. Andrografolid is an active compound from  Andrographis paniculata which has antiproliferation activity of MCF-7 breast cancer cells with IC50 was 61.11 μM. The purpose of this study was to design andrographolide modification structures as human estrogen receptor alpha (hER-α) antagonists. Molecular docking simulation results showed that the andrographolide and AND5 (best andrographolide derivative) have free binding energy (ΔG) values were -9.65 kcal/mol and -12.43 kcal/mol, respectively, and hydrogen bonds were formed with Gly521, Asp351, and Met343. The ΔG value of ANDS was lower than tamoxifen (-11.40 kcal/mol). Pharmacophore modeling results showed that andrographolide and AND5 had a high pharmacophore-fit value of 46.39% and 63.47%, respectively. Molecular dynamics simulation using MM-PBSA calculation method, showed that the hERα-AND5 system has a value of ΔGTOTAL = -50.52 kcal/mol compared to the hERα-estradiol system as an agonist with a value of ∆GTOTAL = -40.86 kcal/mol . These results suggested that AND5 has better affinity for hERα compared to estradiol so that AND5 is a very promising anti breast cancer agent.Keywords: Andrographolide, molecular dynamics, breast cancer, molecular docking, estrogen receptor alpha

Molecular Docking, Drug-Likeness and ADMET Analysis, Application of Density Functional Theory (DFT) and Molecular Dynamics (MD) Simulation to the Phytochemicals from Withania Somnifera as a Potential Antagonist of Estrogen Receptor Alpha (ER-α)

2020 ◽  
Vol 16 ◽  
Author(s):  
Alamgir Hossain
Keyword(s):  
Breast Cancer ◽  
Molecular Dynamics ◽  
Density Functional Theory ◽  
Estrogen Receptor ◽  
Molecular Docking ◽  
Density Functional ◽  
Estrogen Receptor Alpha ◽  
Md Simulation ◽  
Withania Somnifera ◽  
Functional Theory

Introduction: Breast cancer is one of the leading causes of death of women every year. Estrogen receptor alpha (ER-α) is an important pathway that is responsible for the development of breast cancer. Tamoxifen is the most commonly used to treat breast cancer. But the main drawback of using the drug is that it increases the risk of uterine cancer, stroke,and pulmonary embolism. Methods: In this research, the in-silico approach was followed to get the anticancer agent from Withania somnifera as the root extract of the plant is active against breast cancer. For this, 15 bioactive molecules were subjected to molecular docking and got 9 molecules comparing the consensus binding affinity of H3B-9224. Results: After rescoring, drug-likeness analysis, and ADMET analysis of the molecules were done and 3 molecules remained. These 3 molecules showed good ADMET properties which arecrucial requirements in the drug discovery process. Their activity was checked by applying density functional theory (DFT) and all of them showed good reactivity. Their binding interaction was also evaluated. Conclusion: Finally, the stability of those molecules checked by applying molecular dynamics (MD) simulation. After this simulation, 2 molecules remained that had good stability with the protein during the simulation period.

scholarly journals Antagonistic Mechanism of Chalcone Derivatives Against Human Estrogen Alpha of Breast Cancer Using Molecular Dynamic Simulation

2018 ◽  
Vol 34 (6) ◽  
pp. 2735-2741
Author(s):  
Muchtaridi Muchtaridi ◽  
Muhammmad Jajuli ◽  
Muhammad Yusuf
Keyword(s):  
Breast Cancer ◽  
Molecular Dynamics ◽  
Molecular Docking ◽  
Binding Energy ◽  
Computational Simulation ◽  
Docking Simulation ◽  
Breast Adenocarcinoma ◽  
Binding Interaction ◽  
A Value ◽  
Poisson Boltzmann

2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone (ChalcEA) that isolated from Eugenia aquea Burm f. leaves has a potential anticancer activity against human breast adenocarcinoma cell lines (MCF-7). The objective of this study was to modify ChalcEA to increase its activity as an antagonist of breast cancer with computational simulation approach. A molecular docking simulation was done against the modification structure of ChalcEA with Autodock4 to determine binding interaction between ChalcEA and hERα receptor agonists (PDB ID 1g50). Subsequently, the structure with the smallest bond energy value from the docking result was simulated using molecular dynamics to see its stability within a certain time. The results of molecular docking showed that ChalcEA modification which has a phenol group and pyrazole (MK2) had the free binding energy (ΔG) with a value of -10.2 kcal/mol and bonding hydrogen with GLU353 and ARG394, while estradiol had a value of ΔG=-10.7 kcal/mol. Based on molecular dynamics results, the determination of binding energy was gained using MMPBSA (Molecular Mechanics Poisson-Boltzmann and Surface Area) calculation methods. The MK2 has the better affinity than estradiol with a value of ΔGTotal=-45.10 kcal/mol, while estradiol was amounted to -40.86 kcal /mol. This study suggests that the MK2 might be potential as an antagonist to the hERα of breast cancer.

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