PROTAC

From Proteopedia

A Proteolysis-Targeting Chimera (PROTAC) is a small protein with two active domains joined by a linker. PROTACs represent an alternative to conventional enzyme inhibitors, by enabling proteasome induced degradation of the target protein ^[1].

Representative PROTAC from PROTACpedia targeting EGFR Epidermal growth factor receptor P00533. target binding ligandlinkerE3 binder

Predicting PROTACs

PRosettaC ^[2] is a computational resource for the prediction of PROTAC-induced ternary complexes ^[3]. The protocol receives as input, two protein structures (protein target and E3 ligase), including their appropriate ligands (binders), as well as the PROTAC chemical structure in a SMILES representation, and outputs predicted models for the ternary complex.

PROTACpedia

PROTACpedia ^[4] is a collaborative and comprehensive, high-quality and freely accessible resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs). The search can be performed by various parameters such as Target name, UniProt ID, SMILES substructure or by various details regarding a publication.

References

1. ↑ Gadd MS, Testa A, Lucas X, Chan KH, Chen W, Lamont DJ, Zengerle M, Ciulli A. Structural basis of PROTAC cooperative recognition for selective protein degradation. Nat Chem Biol. 2017 Mar 13. doi: 10.1038/nchembio.2329. PMID:28288108 doi:http://dx.doi.org/10.1038/nchembio.2329
2. ↑ PRosettaC https://prosettac.weizmann.ac.il, a computational resource for the prediction of PROTAC-induced ternary complexes.
3. ↑ Zaidman D, Prilusky J, London N. PRosettaC: Rosetta based modeling of PROTAC mediated ternary complexes. J Chem Inf Model. 2020 Sep 25. doi: 10.1021/acs.jcim.0c00589. PMID:32976709 doi:http://dx.doi.org/10.1021/acs.jcim.0c00589
4. ↑ PROTACpedia https://protacpedia.weizmann.ac.il/, a resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs).