Discovery of potential sclerostin inhibitors from plants with loop2 region of sclerostin inhibition by interacting with residues outside Pro-Asn-Ala-Ile-Gly motif
© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Sclerostin, an antagonist of the Wnt/β-catenin signaling pathway, was discovered as a potential therapeutic target for stimulating bone formation in osteoporosis. In this study, molecular docking was employed to predict the...
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th-cmuir.6653943832-654022019-08-05T04:32:50Z Discovery of potential sclerostin inhibitors from plants with loop2 region of sclerostin inhibition by interacting with residues outside Pro-Asn-Ala-Ile-Gly motif Wipawadee Yooin Chalermpong Saenjum Jetsada Ruangsuriya Supat Jiranusornkul Biochemistry, Genetics and Molecular Biology © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Sclerostin, an antagonist of the Wnt/β-catenin signaling pathway, was discovered as a potential therapeutic target for stimulating bone formation in osteoporosis. In this study, molecular docking was employed to predict the binding of 29 herbal compounds, which were reported as bone formation stimulators, to the loop2 region of sclerostin. Then, the 50 ns molecular dynamics (MD) simulation of the complexes between sclerostin and the top 10 hits obtained from molecular docking were carried out. Root mean square deviations (RMSDs) analysis of MD trajectories pointed out that all ligands-complexes remain stable throughout the duration of MD simulations. In addition, the molecular mechanics/generalized born surface area (MM/GBSA) binding free energy and energy decomposition analyses were determined. The results here suggested that baicalin is the most promising inhibitor of sclerostin. Interestingly, baicalin binds to sclerostin via the hydrophobic interaction with the amino acid residues on loop2 region but outside the Pro-Asn-Ala-Ile-Gly (PNAIG) motif, particularly the Arg-Gly-Lys-Trp-Trp-Arg (RGKWWR) motif. This finding could be a novel strategy for developing new sclerostin inhibitors in the future. Communicated by Ramaswamy H. Sarma. 2019-08-05T04:32:50Z 2019-08-05T04:32:50Z 2019-01-01 Journal 15380254 07391102 2-s2.0-85063954610 10.1080/07391102.2019.1599427 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85063954610&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/65402 |
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Biochemistry, Genetics and Molecular Biology Wipawadee Yooin Chalermpong Saenjum Jetsada Ruangsuriya Supat Jiranusornkul Discovery of potential sclerostin inhibitors from plants with loop2 region of sclerostin inhibition by interacting with residues outside Pro-Asn-Ala-Ile-Gly motif |
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© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Sclerostin, an antagonist of the Wnt/β-catenin signaling pathway, was discovered as a potential therapeutic target for stimulating bone formation in osteoporosis. In this study, molecular docking was employed to predict the binding of 29 herbal compounds, which were reported as bone formation stimulators, to the loop2 region of sclerostin. Then, the 50 ns molecular dynamics (MD) simulation of the complexes between sclerostin and the top 10 hits obtained from molecular docking were carried out. Root mean square deviations (RMSDs) analysis of MD trajectories pointed out that all ligands-complexes remain stable throughout the duration of MD simulations. In addition, the molecular mechanics/generalized born surface area (MM/GBSA) binding free energy and energy decomposition analyses were determined. The results here suggested that baicalin is the most promising inhibitor of sclerostin. Interestingly, baicalin binds to sclerostin via the hydrophobic interaction with the amino acid residues on loop2 region but outside the Pro-Asn-Ala-Ile-Gly (PNAIG) motif, particularly the Arg-Gly-Lys-Trp-Trp-Arg (RGKWWR) motif. This finding could be a novel strategy for developing new sclerostin inhibitors in the future. Communicated by Ramaswamy H. Sarma. |
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Wipawadee Yooin Chalermpong Saenjum Jetsada Ruangsuriya Supat Jiranusornkul |
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Wipawadee Yooin Chalermpong Saenjum Jetsada Ruangsuriya Supat Jiranusornkul |
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Wipawadee Yooin |
title |
Discovery of potential sclerostin inhibitors from plants with loop2 region of sclerostin inhibition by interacting with residues outside Pro-Asn-Ala-Ile-Gly motif |
title_short |
Discovery of potential sclerostin inhibitors from plants with loop2 region of sclerostin inhibition by interacting with residues outside Pro-Asn-Ala-Ile-Gly motif |
title_full |
Discovery of potential sclerostin inhibitors from plants with loop2 region of sclerostin inhibition by interacting with residues outside Pro-Asn-Ala-Ile-Gly motif |
title_fullStr |
Discovery of potential sclerostin inhibitors from plants with loop2 region of sclerostin inhibition by interacting with residues outside Pro-Asn-Ala-Ile-Gly motif |
title_full_unstemmed |
Discovery of potential sclerostin inhibitors from plants with loop2 region of sclerostin inhibition by interacting with residues outside Pro-Asn-Ala-Ile-Gly motif |
title_sort |
discovery of potential sclerostin inhibitors from plants with loop2 region of sclerostin inhibition by interacting with residues outside pro-asn-ala-ile-gly motif |
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2019 |
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https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85063954610&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/65402 |
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