High-Throughput Screening and Molecular Dynamics Simulation of Natural Products for the Identification of Anticancer Agents against MCM7 Protein
Minichromosome maintenance complex component 7 (MCM7) belongs to the minichromosome maintenance family that is necessary for the initiation of eukaryotic DNA replication. Overexpression of the MCM7 protein is linked to cellular proliferation and is accountable for critical malignancy in many cancers...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
|
| Series: | Applied Bionics and Biomechanics |
| Online Access: | http://dx.doi.org/10.1155/2022/8308192 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832554750913019904 |
|---|---|
| author | Xin Zhang Hui Chen Hui Lin Ronglan Wen Fan Yang |
| author_facet | Xin Zhang Hui Chen Hui Lin Ronglan Wen Fan Yang |
| author_sort | Xin Zhang |
| collection | DOAJ |
| description | Minichromosome maintenance complex component 7 (MCM7) belongs to the minichromosome maintenance family that is necessary for the initiation of eukaryotic DNA replication. Overexpression of the MCM7 protein is linked to cellular proliferation and is accountable for critical malignancy in many cancers. Mechanistically, the suppression of MCM7 greatly lowers the cellular proliferation associated with cancer. Advances in immunotherapy have revolutionized treatments for many types of cancer. To date, no effective small molecular candidate has been found that can stop the advancement of cancer produced by the MCM7 protein. Here, we present the findings of methods that used a combination of structure-assisted drug design, high-throughput virtual screening, and simulations studies to swiftly generate lead compounds against MCM7 protein. In the current study, we designed efficient compounds that may combat all emerging cancer targeting the common MCM7 protein. For this objective, a molecular docking and molecular dynamics (MD) simulation-based virtual screening of 29,000 NPASS library was carried out. As a consequence of using specific pharmacological, physiological, and ADMET criteria, four new prevailing compounds, NPA000018, NPA000111, NPA00305, and NPA014826, were successfully selected. The MD simulations were also used for a time period of 50 ns to evaluate for stability and dynamics behavior of the compounds. Eventually, compounds NPA000111 and NPA014826 were found to be highly potent against MCM7 protein. According to our results, the selected compounds may be effective in treating certain cancer subtypes, for which additional follow-up experimental validation is recommended. |
| format | Article |
| id | doaj-art-2a510ccb0e70483887d0b4aeb95facc2 |
| institution | Kabale University |
| issn | 1754-2103 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Applied Bionics and Biomechanics |
| spelling | doaj-art-2a510ccb0e70483887d0b4aeb95facc22025-02-03T05:50:36ZengWileyApplied Bionics and Biomechanics1754-21032022-01-01202210.1155/2022/8308192High-Throughput Screening and Molecular Dynamics Simulation of Natural Products for the Identification of Anticancer Agents against MCM7 ProteinXin Zhang0Hui Chen1Hui Lin2Ronglan Wen3Fan Yang4Breast Surgery DepartmentBreast Surgery DepartmentBreast Surgery DepartmentBreast Surgery DepartmentBreast Surgery DepartmentMinichromosome maintenance complex component 7 (MCM7) belongs to the minichromosome maintenance family that is necessary for the initiation of eukaryotic DNA replication. Overexpression of the MCM7 protein is linked to cellular proliferation and is accountable for critical malignancy in many cancers. Mechanistically, the suppression of MCM7 greatly lowers the cellular proliferation associated with cancer. Advances in immunotherapy have revolutionized treatments for many types of cancer. To date, no effective small molecular candidate has been found that can stop the advancement of cancer produced by the MCM7 protein. Here, we present the findings of methods that used a combination of structure-assisted drug design, high-throughput virtual screening, and simulations studies to swiftly generate lead compounds against MCM7 protein. In the current study, we designed efficient compounds that may combat all emerging cancer targeting the common MCM7 protein. For this objective, a molecular docking and molecular dynamics (MD) simulation-based virtual screening of 29,000 NPASS library was carried out. As a consequence of using specific pharmacological, physiological, and ADMET criteria, four new prevailing compounds, NPA000018, NPA000111, NPA00305, and NPA014826, were successfully selected. The MD simulations were also used for a time period of 50 ns to evaluate for stability and dynamics behavior of the compounds. Eventually, compounds NPA000111 and NPA014826 were found to be highly potent against MCM7 protein. According to our results, the selected compounds may be effective in treating certain cancer subtypes, for which additional follow-up experimental validation is recommended.http://dx.doi.org/10.1155/2022/8308192 |
| spellingShingle | Xin Zhang Hui Chen Hui Lin Ronglan Wen Fan Yang High-Throughput Screening and Molecular Dynamics Simulation of Natural Products for the Identification of Anticancer Agents against MCM7 Protein Applied Bionics and Biomechanics |
| title | High-Throughput Screening and Molecular Dynamics Simulation of Natural Products for the Identification of Anticancer Agents against MCM7 Protein |
| title_full | High-Throughput Screening and Molecular Dynamics Simulation of Natural Products for the Identification of Anticancer Agents against MCM7 Protein |
| title_fullStr | High-Throughput Screening and Molecular Dynamics Simulation of Natural Products for the Identification of Anticancer Agents against MCM7 Protein |
| title_full_unstemmed | High-Throughput Screening and Molecular Dynamics Simulation of Natural Products for the Identification of Anticancer Agents against MCM7 Protein |
| title_short | High-Throughput Screening and Molecular Dynamics Simulation of Natural Products for the Identification of Anticancer Agents against MCM7 Protein |
| title_sort | high throughput screening and molecular dynamics simulation of natural products for the identification of anticancer agents against mcm7 protein |
| url | http://dx.doi.org/10.1155/2022/8308192 |
| work_keys_str_mv | AT xinzhang highthroughputscreeningandmoleculardynamicssimulationofnaturalproductsfortheidentificationofanticanceragentsagainstmcm7protein AT huichen highthroughputscreeningandmoleculardynamicssimulationofnaturalproductsfortheidentificationofanticanceragentsagainstmcm7protein AT huilin highthroughputscreeningandmoleculardynamicssimulationofnaturalproductsfortheidentificationofanticanceragentsagainstmcm7protein AT ronglanwen highthroughputscreeningandmoleculardynamicssimulationofnaturalproductsfortheidentificationofanticanceragentsagainstmcm7protein AT fanyang highthroughputscreeningandmoleculardynamicssimulationofnaturalproductsfortheidentificationofanticanceragentsagainstmcm7protein |