Systemic evolutionary chemical space exploration for drug discovery
Open accessPublished version of a preprint
Abstract
Chemical space exploration is a major task of the hit-finding process during the pursuit of novel chemical entities. Compared with other screening technologies, computational de novo design has become a popular approach to overcome the limitation of current chemical libraries. Here, we reported a de novo design platform named systemic evolutionary chemical space explorer (SECSE). The platform was conceptually inspired by fragment-based drug design, that miniaturized a “lego-building” process within the pocket of a certain target. The key to virtual hits generation was then turned into a computational search problem. To enhance search and optimization, human intelligence and deep learning were integrated. Application of SECSE against phosphoglycerate dehydrogenase (PHGDH), proved its potential in finding novel and diverse small molecules that are attractive starting points for further validation. This platform is open-sourced and the code is available at http://github.com/KeenThera/SECSE.
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- Authors
- Lu, C., Liu, S., Shi, W., Yu, J., Zhou, Z., Zhang, X., Lu, X., Cai, F., Xia, N., & Wang, Y.
- Corresponding author
- Wang, Yikai
- Venue
- Journal of Cheminformatics
- Published
- 2022-04-01
- Volume
- 14
- Issue
- 1
- Pages
- 19-19
- ISSN
- 1758-2946 (ISSN-L)
- PMC
- PMC8973791
- OpenAlex
- W4225835448
- Cited by
- 30
- References
- 6
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 11 · 2023: 5
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Cheminformatics (publishedVersion, cc-by)
- ChemRxiv (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and Characterization of Heterocyclic Compounds
- Keywords
- de novo drug design, chemical space exploration, fragment-based drug discovery, PHGDH, deep learning, human-in-the-loop, open source software, hit finding
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