Finding the molecular scaffold of nuclear receptor inhibitors through high-throughput screening based on proteochemometric modelling
Abstract Nuclear receptors (NR) are a class of proteins that are responsible for sensing steroid and thyroid hormones and certain other molecules. In that case, NR have the ability to regulate the expression of specific genes and associated with various diseases, which make it essential drug targets...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-04-01
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| Series: | Journal of Cheminformatics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13321-018-0275-x |
| _version_ | 1811215857670422528 |
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| author | Tianyi Qiu Dingfeng Wu Jingxuan Qiu Zhiwei Cao |
| author_facet | Tianyi Qiu Dingfeng Wu Jingxuan Qiu Zhiwei Cao |
| author_sort | Tianyi Qiu |
| collection | DOAJ |
| description | Abstract Nuclear receptors (NR) are a class of proteins that are responsible for sensing steroid and thyroid hormones and certain other molecules. In that case, NR have the ability to regulate the expression of specific genes and associated with various diseases, which make it essential drug targets. Approaches which can predict the inhibition ability of compounds for different NR target should be particularly helpful for drug development. In this study, proteochemometric modelling was introduced to analysis the bioactivity between chemical compounds and NR targets. Results illustrated the ability of our PCM model for high-throughput NR-inhibitor screening after evaluated on both internal (AUC > 0.870) and external (AUC > 0.746) validation set. Moreover, in-silico predicted bioactive compounds were clustered according to structure similarity and a series of representative molecular scaffolds can be derived for five major NR targets. Through scaffolds analysis, those essential bioactive scaffolds of different NR target can be detected and compared. Generally, the methods and molecular scaffolds proposed in this article can not only help the screening of potential therapeutic NR-inhibitors but also able to guide the future NR-related drug discovery. |
| first_indexed | 2024-04-12T06:30:33Z |
| format | Article |
| id | doaj.art-b67d0f8b54024fc98e22b6817ac167c4 |
| institution | Directory Open Access Journal |
| issn | 1758-2946 |
| language | English |
| last_indexed | 2024-04-12T06:30:33Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Cheminformatics |
| spelling | doaj.art-b67d0f8b54024fc98e22b6817ac167c42022-12-22T03:44:02ZengBMCJournal of Cheminformatics1758-29462018-04-011011910.1186/s13321-018-0275-xFinding the molecular scaffold of nuclear receptor inhibitors through high-throughput screening based on proteochemometric modellingTianyi Qiu0Dingfeng Wu1Jingxuan Qiu2Zhiwei Cao3School of Life Sciences and Technology, Shanghai 10th People’s Hospital, Tongji UniversitySchool of Life Sciences and Technology, Shanghai 10th People’s Hospital, Tongji UniversitySchool of Life Sciences and Technology, Shanghai 10th People’s Hospital, Tongji UniversitySchool of Life Sciences and Technology, Shanghai 10th People’s Hospital, Tongji UniversityAbstract Nuclear receptors (NR) are a class of proteins that are responsible for sensing steroid and thyroid hormones and certain other molecules. In that case, NR have the ability to regulate the expression of specific genes and associated with various diseases, which make it essential drug targets. Approaches which can predict the inhibition ability of compounds for different NR target should be particularly helpful for drug development. In this study, proteochemometric modelling was introduced to analysis the bioactivity between chemical compounds and NR targets. Results illustrated the ability of our PCM model for high-throughput NR-inhibitor screening after evaluated on both internal (AUC > 0.870) and external (AUC > 0.746) validation set. Moreover, in-silico predicted bioactive compounds were clustered according to structure similarity and a series of representative molecular scaffolds can be derived for five major NR targets. Through scaffolds analysis, those essential bioactive scaffolds of different NR target can be detected and compared. Generally, the methods and molecular scaffolds proposed in this article can not only help the screening of potential therapeutic NR-inhibitors but also able to guide the future NR-related drug discovery.http://link.springer.com/article/10.1186/s13321-018-0275-xProteochemometric modellingNuclear receptorMolecular scaffoldCheminformatics |
| spellingShingle | Tianyi Qiu Dingfeng Wu Jingxuan Qiu Zhiwei Cao Finding the molecular scaffold of nuclear receptor inhibitors through high-throughput screening based on proteochemometric modelling Journal of Cheminformatics Proteochemometric modelling Nuclear receptor Molecular scaffold Cheminformatics |
| title | Finding the molecular scaffold of nuclear receptor inhibitors through high-throughput screening based on proteochemometric modelling |
| title_full | Finding the molecular scaffold of nuclear receptor inhibitors through high-throughput screening based on proteochemometric modelling |
| title_fullStr | Finding the molecular scaffold of nuclear receptor inhibitors through high-throughput screening based on proteochemometric modelling |
| title_full_unstemmed | Finding the molecular scaffold of nuclear receptor inhibitors through high-throughput screening based on proteochemometric modelling |
| title_short | Finding the molecular scaffold of nuclear receptor inhibitors through high-throughput screening based on proteochemometric modelling |
| title_sort | finding the molecular scaffold of nuclear receptor inhibitors through high throughput screening based on proteochemometric modelling |
| topic | Proteochemometric modelling Nuclear receptor Molecular scaffold Cheminformatics |
| url | http://link.springer.com/article/10.1186/s13321-018-0275-x |
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