Related Experiment Video
Updated: Aug 4, 2025
Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Integrated virtual screening and molecular dynamics simulation approaches revealed potential natural inhibitors for
Yasir Bashir1, Fatima Noor1, Sajjad Ahmad2
1Integrative Omics and Molecular Modeling Laboratory, Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.
Abstract:
Triple negative breast cancers (TNBC) are clinically heterogeneous but mostly aggressive malignancies devoid of expression of the estrogen, progesterone, and HER2 (ERBB2 or NEU) receptors. It accounts for 15-20% of all cases. Altered epigenetic regulation including DNA hypermethylation by DNA methyltransferase 1 (DNMT1) has been implicated as one of the causes of TNBC tumorigenesis. The antitumor effect of DNMT1 has also been explored in TNBC that currently lacks targeted therapies. However, the actual treatment for TNBC is yet to be discovered. This study is attributed to the identification of novel drug targets against TNBC. A comprehensive docking and simulation analysis was performed to optimize promising new compounds by estimating their binding affinity to the target protein. Molecular dynamics simulation of 500 ns well complemented the binding affinity of the compound and revealed strong stability of predicted compounds at the docked site. Calculation of binding free energies using MMPBSA and MMGBSA validated the strong binding affinity between compound and binding pockets of DNMT1. In a nutshell, our study uncovered that Beta-Mangostin, Gancaonin Z, 5-hydroxysophoranone, Sophoraflavanone L, and Dorsmanin H showed maximum binding affinity with the active sites of DNMT1. Furthermore, all of these compounds depict maximum drug-like properties. Therefore, the proposed compounds can be a potential candidate for patients with TNBC, but, experimental validation is needed to ensure their safety.Communicated by Ramaswamy H. Sarma.
Insights
Researchers identified potential new drug candidates for triple-negative breast cancer (TNBC). Computational analysis revealed that compounds like Beta-Mangostin strongly bind to DNMT1, a key protein in TNBC development, offering hope for new treatments.
Area of Science:
- Oncology
- Biochemistry
- Computational Biology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive malignancy lacking targeted therapies.
- Epigenetic alterations, including DNA hypermethylation by DNA methyltransferase 1 (DNMT1), contribute to TNBC.
- There is a critical need for novel therapeutic strategies against TNBC.
Purpose of the Study:
- To identify novel drug targets and potential therapeutic compounds for TNBC.
- To investigate the binding affinity of various compounds to DNMT1 using computational methods.
Main Methods:
- Comprehensive molecular docking and simulation analyses were performed.
- 500 ns molecular dynamics simulations were utilized to assess compound stability.
- Binding free energies were calculated using MMPBSA and MMGBSA methods.
Main Results:
- Beta-Mangostin, Gancaonin Z, 5-hydroxysophoranone, Sophoraflavanone L, and Dorsmanin H exhibited strong binding affinity to DNMT1 active sites.
- Molecular dynamics simulations confirmed the stability of these compounds at the docked site.
- All identified compounds demonstrated favorable drug-like properties.
Conclusions:
- The identified compounds show potential as therapeutic candidates for TNBC.
- Further experimental validation is required to confirm the safety and efficacy of these compounds.
More Related Videos
10:29Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
07:41Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019