A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen Years
Structure-based virtual screening (SBVS), also known as molecular docking, has been increasingly applied to discover small-molecule ligands based on the protein structures in the early stage of drug discovery. In this review, we comprehensively surveyed the prospective applications of molecular dock...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/24/15961 |
| _version_ | 1797457296206331904 |
|---|---|
| author | Hui Zhu Yulin Zhang Wei Li Niu Huang |
| author_facet | Hui Zhu Yulin Zhang Wei Li Niu Huang |
| author_sort | Hui Zhu |
| collection | DOAJ |
| description | Structure-based virtual screening (SBVS), also known as molecular docking, has been increasingly applied to discover small-molecule ligands based on the protein structures in the early stage of drug discovery. In this review, we comprehensively surveyed the prospective applications of molecular docking judged by solid experimental validations in the literature over the past fifteen years. Herein, we systematically analyzed the novelty of the targets and the docking hits, practical protocols of docking screening, and the following experimental validations. Among the 419 case studies we reviewed, most virtual screenings were carried out on widely studied targets, and only 22% were on less-explored new targets. Regarding docking software, GLIDE is the most popular one used in molecular docking, while the DOCK 3 series showed a strong capacity for large-scale virtual screening. Besides, the majority of identified hits are promising in structural novelty and one-quarter of the hits showed better potency than 1 μM, indicating that the primary advantage of SBVS is to discover new chemotypes rather than highly potent compounds. Furthermore, in most studies, only in vitro bioassays were carried out to validate the docking hits, which might limit the further characterization and development of the identified active compounds. Finally, several successful stories of SBVS with extensive experimental validations have been highlighted, which provide unique insights into future SBVS drug discovery campaigns. |
| first_indexed | 2024-03-09T16:19:12Z |
| format | Article |
| id | doaj.art-e078233d562d497dab6244192ec33973 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:19:12Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e078233d562d497dab6244192ec339732023-11-24T15:30:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241596110.3390/ijms232415961A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen YearsHui Zhu0Yulin Zhang1Wei Li2Niu Huang3Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 102206, ChinaTsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 102206, ChinaRPXDs (Suzhou) Co., Ltd., Suzhou 215028, ChinaTsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 102206, ChinaStructure-based virtual screening (SBVS), also known as molecular docking, has been increasingly applied to discover small-molecule ligands based on the protein structures in the early stage of drug discovery. In this review, we comprehensively surveyed the prospective applications of molecular docking judged by solid experimental validations in the literature over the past fifteen years. Herein, we systematically analyzed the novelty of the targets and the docking hits, practical protocols of docking screening, and the following experimental validations. Among the 419 case studies we reviewed, most virtual screenings were carried out on widely studied targets, and only 22% were on less-explored new targets. Regarding docking software, GLIDE is the most popular one used in molecular docking, while the DOCK 3 series showed a strong capacity for large-scale virtual screening. Besides, the majority of identified hits are promising in structural novelty and one-quarter of the hits showed better potency than 1 μM, indicating that the primary advantage of SBVS is to discover new chemotypes rather than highly potent compounds. Furthermore, in most studies, only in vitro bioassays were carried out to validate the docking hits, which might limit the further characterization and development of the identified active compounds. Finally, several successful stories of SBVS with extensive experimental validations have been highlighted, which provide unique insights into future SBVS drug discovery campaigns.https://www.mdpi.com/1422-0067/23/24/15961structure-based virtual screeningmolecular dockingstructural novelty |
| spellingShingle | Hui Zhu Yulin Zhang Wei Li Niu Huang A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen Years International Journal of Molecular Sciences structure-based virtual screening molecular docking structural novelty |
| title | A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen Years |
| title_full | A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen Years |
| title_fullStr | A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen Years |
| title_full_unstemmed | A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen Years |
| title_short | A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen Years |
| title_sort | comprehensive survey of prospective structure based virtual screening for early drug discovery in the past fifteen years |
| topic | structure-based virtual screening molecular docking structural novelty |
| url | https://www.mdpi.com/1422-0067/23/24/15961 |
| work_keys_str_mv | AT huizhu acomprehensivesurveyofprospectivestructurebasedvirtualscreeningforearlydrugdiscoveryinthepastfifteenyears AT yulinzhang acomprehensivesurveyofprospectivestructurebasedvirtualscreeningforearlydrugdiscoveryinthepastfifteenyears AT weili acomprehensivesurveyofprospectivestructurebasedvirtualscreeningforearlydrugdiscoveryinthepastfifteenyears AT niuhuang acomprehensivesurveyofprospectivestructurebasedvirtualscreeningforearlydrugdiscoveryinthepastfifteenyears AT huizhu comprehensivesurveyofprospectivestructurebasedvirtualscreeningforearlydrugdiscoveryinthepastfifteenyears AT yulinzhang comprehensivesurveyofprospectivestructurebasedvirtualscreeningforearlydrugdiscoveryinthepastfifteenyears AT weili comprehensivesurveyofprospectivestructurebasedvirtualscreeningforearlydrugdiscoveryinthepastfifteenyears AT niuhuang comprehensivesurveyofprospectivestructurebasedvirtualscreeningforearlydrugdiscoveryinthepastfifteenyears |