Computer aided drug design in the development of proteolysis targeting chimeras.
| Autor: | Tunjic TM; Celeris Therapeutics GmbH, Schmiedlstraße 3, 8042 Graz, Austria., Weber N; Celeris Therapeutics GmbH, Schmiedlstraße 3, 8042 Graz, Austria., Brunsteiner M; Celeris Therapeutics GmbH, Schmiedlstraße 3, 8042 Graz, Austria. |
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| Jazyk: | angličtina |
| Zdroj: | Computational and structural biotechnology journal [Comput Struct Biotechnol J] 2023 Feb 24; Vol. 21, pp. 2058-2067. Date of Electronic Publication: 2023 Feb 24 (Print Publication: 2023). |
| DOI: | 10.1016/j.csbj.2023.02.042 |
| Abstrakt: | Proteolysis targeting chimeras represent a class of drug molecules with a number of attractive properties, most notably a potential to work for targets that, so far, have been in-accessible for conventional small molecule inhibitors. Due to their different mechanism of action, and physico-chemical properties, many of the methods that have been designed and applied for computer aided design of traditional small molecule drugs are not applicable for proteolysis targeting chimeras. Here we review recent developments in this field focusing on three aspects: de-novo linker-design, estimation of absorption for beyond-rule-of-5 compounds, and the generation and ranking of ternary complex structures. In spite of this field still being young, we find that a good number of models and algorithms are available, with the potential to assist the design of such compounds in-silico, and accelerate applied pharmaceutical research. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2023 The Author(s).) |
| Databáze: | MEDLINE |
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