Multitarget-Based Virtual Screening for Identification of Herbal Substances toward Potential Osteoclastic Targets
Osteoporosis is a complex bone disease indicating porous bone with low bone mass density and fragility. Cathepsin K, V-ATPase, and α<sub>V</sub>β<sub>3</sub> integrin are exhibited as novel targets for osteoporosis treatment. Our preliminary study uses a state-of-the-art meth...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
|
| Series: | Applied Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3417/12/5/2621 |
| _version_ | 1797475628147015680 |
|---|---|
| author | Siripat Chaichit Pathomwat Wongrattanakamon Busaban Sirithunyalug Piyarat Nimmanpipug Supat Jiranusornkul |
| author_facet | Siripat Chaichit Pathomwat Wongrattanakamon Busaban Sirithunyalug Piyarat Nimmanpipug Supat Jiranusornkul |
| author_sort | Siripat Chaichit |
| collection | DOAJ |
| description | Osteoporosis is a complex bone disease indicating porous bone with low bone mass density and fragility. Cathepsin K, V-ATPase, and α<sub>V</sub>β<sub>3</sub> integrin are exhibited as novel targets for osteoporosis treatment. Our preliminary study uses a state-of-the-art method, including target-based virtual screening and clustering methods to determine promising candidates with multitarget properties. Phytochemicals with osteoprotective properties from the literature are used to elucidate the molecular interactions toward three targets. The binding scores of compounds are normalized and rescored. The K-means and hierarchical clustering methods are applied to filter and define the promising compounds, and the silhouette analysis is supposed to validate the clustering method. We explore 108 herbal compounds by virtual screening and the cluster approach, and find that rutin, sagittatoside A, icariin, and kaempferitrin showed strong binding affinities against Cathepsin K, V-ATPase, and α<sub>V</sub>β<sub>3</sub> integrin. Dockings of candidates toward three targets also provide the protein-ligand interactions and crucial amino acids for binding. Our study provides a straightforward and less time-consuming approach to exploring the new multitarget candidates for further investigations, using a combination of in silico methods. |
| first_indexed | 2024-03-09T20:46:52Z |
| format | Article |
| id | doaj.art-9997f572126d4bca9b2ffa6adbe79b7f |
| institution | Directory Open Access Journal |
| issn | 2076-3417 |
| language | English |
| last_indexed | 2024-03-09T20:46:52Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Applied Sciences |
| spelling | doaj.art-9997f572126d4bca9b2ffa6adbe79b7f2023-11-23T22:43:41ZengMDPI AGApplied Sciences2076-34172022-03-01125262110.3390/app12052621Multitarget-Based Virtual Screening for Identification of Herbal Substances toward Potential Osteoclastic TargetsSiripat Chaichit0Pathomwat Wongrattanakamon1Busaban Sirithunyalug2Piyarat Nimmanpipug3Supat Jiranusornkul4PhD Degree Program in Pharmacy, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, ThailandLaboratory of Molecular Design and Modeling (LMDS), Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, ThailandLaboratory of Molecular Design and Modeling (LMDS), Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, ThailandFaculty of Science, Chiang Mai University, Chiang Mai 50200, ThailandLaboratory of Molecular Design and Modeling (LMDS), Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, ThailandOsteoporosis is a complex bone disease indicating porous bone with low bone mass density and fragility. Cathepsin K, V-ATPase, and α<sub>V</sub>β<sub>3</sub> integrin are exhibited as novel targets for osteoporosis treatment. Our preliminary study uses a state-of-the-art method, including target-based virtual screening and clustering methods to determine promising candidates with multitarget properties. Phytochemicals with osteoprotective properties from the literature are used to elucidate the molecular interactions toward three targets. The binding scores of compounds are normalized and rescored. The K-means and hierarchical clustering methods are applied to filter and define the promising compounds, and the silhouette analysis is supposed to validate the clustering method. We explore 108 herbal compounds by virtual screening and the cluster approach, and find that rutin, sagittatoside A, icariin, and kaempferitrin showed strong binding affinities against Cathepsin K, V-ATPase, and α<sub>V</sub>β<sub>3</sub> integrin. Dockings of candidates toward three targets also provide the protein-ligand interactions and crucial amino acids for binding. Our study provides a straightforward and less time-consuming approach to exploring the new multitarget candidates for further investigations, using a combination of in silico methods.https://www.mdpi.com/2076-3417/12/5/2621Cathepsin KV-ATPaseintegrinvirtual screeningmultitarget |
| spellingShingle | Siripat Chaichit Pathomwat Wongrattanakamon Busaban Sirithunyalug Piyarat Nimmanpipug Supat Jiranusornkul Multitarget-Based Virtual Screening for Identification of Herbal Substances toward Potential Osteoclastic Targets Applied Sciences Cathepsin K V-ATPase integrin virtual screening multitarget |
| title | Multitarget-Based Virtual Screening for Identification of Herbal Substances toward Potential Osteoclastic Targets |
| title_full | Multitarget-Based Virtual Screening for Identification of Herbal Substances toward Potential Osteoclastic Targets |
| title_fullStr | Multitarget-Based Virtual Screening for Identification of Herbal Substances toward Potential Osteoclastic Targets |
| title_full_unstemmed | Multitarget-Based Virtual Screening for Identification of Herbal Substances toward Potential Osteoclastic Targets |
| title_short | Multitarget-Based Virtual Screening for Identification of Herbal Substances toward Potential Osteoclastic Targets |
| title_sort | multitarget based virtual screening for identification of herbal substances toward potential osteoclastic targets |
| topic | Cathepsin K V-ATPase integrin virtual screening multitarget |
| url | https://www.mdpi.com/2076-3417/12/5/2621 |
| work_keys_str_mv | AT siripatchaichit multitargetbasedvirtualscreeningforidentificationofherbalsubstancestowardpotentialosteoclastictargets AT pathomwatwongrattanakamon multitargetbasedvirtualscreeningforidentificationofherbalsubstancestowardpotentialosteoclastictargets AT busabansirithunyalug multitargetbasedvirtualscreeningforidentificationofherbalsubstancestowardpotentialosteoclastictargets AT piyaratnimmanpipug multitargetbasedvirtualscreeningforidentificationofherbalsubstancestowardpotentialosteoclastictargets AT supatjiranusornkul multitargetbasedvirtualscreeningforidentificationofherbalsubstancestowardpotentialosteoclastictargets |