PROTAC

From Proteopedia

spinqualitylabelsall models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image 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]. PROTAC Target Structure BRAF kinase domain 6uuo BRD9 bromodomain 6hm0 Cereblon 6r0q, 6r0u, 6r0v, 6r11, 6r12, 6r13, 6r18, 6r19, 6r1a, 6r1c, 6r1d, 6r1k, 6r1w, 6r1x DDB1-CRBN-BRD4(BD1) 6bn7, 6bn8, 6bn9, 6bnb, 6boy SMARCA2, SMARCA4 6hr2 Predicting PROTAC-induced ternary complexes PRosettaC [2] is a computational resource for the prediction of PROTAC-induced ternary complexes [3]. PRosettaC 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. Other methods become available [4][5]. PROTACpedia Representative PROTAC from PROTACpedia targeting EGFR Epidermal growth factor receptor P00533. target binding ligandlinkerE3 binder PROTACpedia [6] 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. ↑ Drummond ML, Henry A, Li H, Williams CI. Improved Accuracy for Modeling PROTAC-Mediated Ternary Complex Formation and Targeted Protein Degradation via New In Silico Methodologies. J Chem Inf Model. 2020 Oct 26;60(10):5234-5254. doi: 10.1021/acs.jcim.0c00897., Epub 2020 Oct 12. PMID:32969649 doi:http://dx.doi.org/10.1021/acs.jcim.0c00897
5. ↑ Bai N, Miller SA, Andrianov GV, Yates M, Kirubakaran P, Karanicolas J. Rationalizing PROTAC-Mediated Ternary Complex Formation Using Rosetta. J Chem Inf Model. 2021 Feb 24. doi: 10.1021/acs.jcim.0c01451. PMID:33625214 doi:http://dx.doi.org/10.1021/acs.jcim.0c01451
6. ↑ PROTACpedia https://protacpedia.weizmann.ac.il/, a resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs).