Improved Accuracy for Modeling PROTAC-Mediated Ternary Complex Formation and Targeted Protein Degradation via New In Silico Methodologies
Open accessPublished version of a preprint
Abstract
Extending upon our previous publication [Drummond, M. ; et al.J. Chem. Inf. Model.2019, 59, 1634−1644], two additional computational methods are presented to model PROTAC-mediated ternary complex structures, which are then used to predict the efficacy of any accompanying protein degradation. Method 4B, an extension to one of our previous approaches, incorporates a clustering procedure uniquely suited for considering ternary complexes. Method 4B yields the highest proportion to date of crystal-like poses in modeled ternary complex ensembles, nearing 100% in two cases and always giving a hit rate of at least 10%. Techniques to further improve this performance for particularly troublesome cases are suggested and validated. This demonstrated ability to reliably reproduce known crystallographic ternary complex structures is further established through modeling of a newly released crystal structure. Moreover, for the far more common scenario where the structure of the ternary complex intermediate is unknown, the methods detailed in this work nonetheless consistently yield results that reliably follow experimental protein degradation trends, as established through seven retrospective case studies. These various case studies cover challenging yet common modeling situations, such as when the precise orientation of the PROTAC binding moiety in one (or both) of the protein pockets has not been experimentally established. Successful results are presented for one PROTAC targeting many proteins, for different PROTACs targeting the same protein, and even for degradation effected by an E3 ligase that has not been structurally characterized in a ternary complex. Overall, the computational modeling approaches detailed in this work should greatly facilitate PROTAC screening and design efforts, so that the many advantages of a PROTAC-based degradation approach can be effectively utilized both rapidly and at reduced cost.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Drummond and Williams proposed four methods combining linker conformational searches with protein-protein docking, leading to virtual models of ternary complexes resembling known crystal structures.
“Soon after, Drummond and Williams proposed four methods that combined linker conformational searches with protein-protein docking, leading to virtual models of ternary complexes that resembled known crystal structures.174,175”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [174]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
SMARCAD1 ATPase activity is required to silence endogenous retroviruses in embryonic stem cells
Sachs, P., Ding, D., Bergmaier, P., Lamp, B., Schlagheck, C., Finkernagel, F., Nist, A., Stiewe, T., & Mermoud, J. E. (2019) · Nature Communications · doi:10.1038/s41467-019-09078-0 · Cited by 2,388 · see citing works
Catalytic in vivo protein knockdown by small-molecule PROTACs
Bondeson, D. P., Mares, A., Smith, I. E. D., Ko, E., Campos, S., Miah, A. H., Mulholland, K. E., Routly, N., Buckley, D. L., Gustafson, J. L., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1858 · Cited by 1,356 · see citing works
Structural basis of PROTAC cooperative recognition for selective protein degradation
Gadd, M. S., Testa, A., Lucas, X., Chan, K.-H., Chen, W., Lamont, D. J., Zengerle, M., & Ciulli, A. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2329 · Cited by 1,242 · see citing works
Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery
Burslem, G. M., & Crews, C. M. (2020) · Cell · doi:10.1016/j.cell.2019.11.031 · Cited by 1,079 · see citing works
Consolidation alters motor sequence-specific distributed representations
Pinsard, B., Boutin, A., Gabitov, E., Lungu, O., Benali, H., & Doyon, J. (2019) · eLife · doi:10.7554/elife.39324 · Cited by 1,066 · see citing works
Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4
Zengerle, M., Chan, K.-H., & Ciulli, A. (2015) · ACS Chemical Biology · doi:10.1021/acschembio.5b00216 · Cited by 1,056 · see citing works
Targeted protein degradation: expanding the toolbox
Schapira, M., Calabrese, M. F., Bullock, A. N., & Crews, C. M. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0047-y · Cited by 960 · see citing works
The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study
Burslem, G. M., Smith, B. E., Lai, A. C., Jaime-Figueroa, S., McQuaid, D. C., Bondeson, D. P., Toure, M., Dong, H., Qian, Y., Wang, J., et al. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.09.009 · Cited by 686 · see citing works
PROTACs: great opportunities for academia and industry
Sun, X., Gao, H., Yang, Y., He, M., Wu, Y., Song, Y.-G., Tong, Y., & Rao, Y. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0101-6 · Cited by 651 · see citing works
Modular PROTAC design for the degradation of oncogenic BCR-ABL
Lai, A. C., Toure, M., Hellerschmied, D., Salami, J., Jaime‐Figueroa, S., Ko, E., Hines, J., & Crews, C. M. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201507634 · Cited by 618 · see citing works
Plasticity in binding confers selectivity in ligand-induced protein degradation
Nowak, R. P., DeAngelo, S. L., Buckley, D., He, Z., Donovan, K. A., An, J., Safaee, N., Jedrychowski, M. P., Ponthier, C. M., Ishoey, M., et al. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0055-y · Cited by 615 · see citing works
BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design
Farnaby, W., Koegl, M., Roy, M. J., Whitworth, C., Diers, E., Trainor, N., Zollman, D., Steurer, S., Karolyi-Oezguer, J., Riedmueller, C., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0294-6 · Cited by 562 · see citing works
Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase
Smith, B. E., Wang, S. L., Jaime-Figueroa, S., Harbin, A., Wang, J., Hamman, B. D., & Crews, C. M. (2019) · Nature Communications · doi:10.1038/s41467-018-08027-7 · Cited by 517 · see citing works
Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16
Zhang, X., Crowley, V. M., Wucherpfennig, T. G., Dix, M. M., & Cravatt, B. F. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0279-5 · Cited by 487 · see citing works
Variability in docking success rates due to dataset preparation.
Corbeil, C. R., Williams, C. I., & Labute, P. (2012) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-012-9570-1 · Cited by 469 · see citing works
Self-citationA Chemoproteomic Approach to Query the Degradable Kinome Using a Multi-kinase Degrader
Huang, H.-T., Dobrovolsky, D., Paulk, J., Yang, G., Weisberg, E. L., Doctor, Z. M., Buckley, D. L., Cho, J.-H., Ko, E., Jang, J., et al. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.10.005 · Cited by 437 · see citing works
Harnessing the anti-cancer natural product nimbolide for targeted protein degradation
Spradlin, J. N., Hu, X., Ward, C. C., Brittain, S. M., Jones, M. D., Ou, L., To, M., Proudfoot, A., Ornelas, E., Woldegiorgis, M., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0304-8 · Cited by 432 · see citing works
Edmondson, S. D., Yang, B., & Fallan, C. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.04.030 · Cited by 422 · see citing works
Delineating the role of cooperativity in the design of potent PROTACs for BTK
Zorba, A., Nguyen, C., Xu, Y., Starr, J., Borzilleri, K., Smith, J., Zhu, H., Farley, K. A., Ding, W., Schiemer, J., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1803662115 · Cited by 419 · see citing works
Itoh, Y., Ishikawa, M., Naito, M., & Hashimoto, Y. (2010) · Journal of the American Chemical Society · doi:10.1021/ja100691p · Cited by 404 · see citing works
Buhimschi, A. D., Armstrong, H. A., Toure, M., Jaime-Figueroa, S., Chen, T. L., Lehman, A. M., Woyach, J. A., Johnson, A. J., Byrd, J. C., & Crews, C. M. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b00391 · Cited by 394 · see citing works
Light-Induced Protein Degradation with Photocaged PROTACs
Xue, G., Wang, K., Zhou, D., Zhong, H., & Pan, Z. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b06422 · Cited by 377 · see citing works
Zhang, L., Riley-Gillis, B., Vijay, P., & Shen, Y. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-1129 · Cited by 365 · see citing works
Hines, J., Lartigue, S., Dong, H., Qian, Y., & Crews, C. M. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-2918 · Cited by 348 · see citing works
Assessment of CAPRI predictions in rounds 3–5 shows progress in docking procedures
Méndez, R., Leplae, R., Lensink, M. F., & Wodak, S. J. (2005) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20551 · Cited by 340 · see citing works
Ward, C. C., Kleinman, J. I., Brittain, S. M., Lee, P. S., Chung, C. Y. S., Kim, K., Petri, Y., Thomas, J. R., Tallarico, J. A., McKenna, J. M., et al. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.8b01083 · Cited by 336 · see citing works
PHOTACs enable optical control of protein degradation
Reynders, M., Matsuura, B. S., Bérouti, M., Simoneschi, D., Marzio, A., Pagano, M., & Trauner, D. H. (2020) · Science Advances · doi:10.1126/sciadv.aay5064 · Cited by 333 · see citing works
Labute, P. (2010) · Journal of Chemical Information and Modeling · doi:10.1021/ci900508k · Cited by 328 · see citing works
Reversible Spatiotemporal Control of Induced Protein Degradation by Bistable PhotoPROTACs
Pfaff, P., Samarasinghe, K. T. G., Crews, C. M., & Carreira, E. M. (2019) · ACS Central Science · doi:10.1021/acscentsci.9b00713 · Cited by 314 · see citing works
Li, Y., Yang, J., Aguilar, A., McEachern, D., Przybranowski, S., Liu, L., Yang, C.-Y., Wang, M., Han, X., & Wang, S. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00909 · Cited by 312 · see citing works
Light-induced control of protein destruction by opto-PROTAC
Liu, J., Chen, H., Ma, L., He, Z., Wang, D., Liu, Y., Lin, Q., Zhang, T., Gray, N. S., Kanıskan, H. Ü., et al. (2020) · Science Advances · doi:10.1126/sciadv.aay5154 · Cited by 305 · see citing works
Deficiency of TRPM2 leads to embryonic neurogenesis defects in hyperthermia
Li, Y., & Jiao, J. (2020) · Science Advances · doi:10.1126/sciadv.aay6350 · Cited by 290 · see citing works
Targeted degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models
Silva, M. C., Ferguson, F. M., Cai, Q., Donovan, K. A., Nandi, G., Patnaik, D., Zhang, T., Huang, H.-T., Lucente, D. E., Dickerson, B. C., et al. (2019) · eLife · doi:10.7554/elife.45457 · Cited by 283 · see citing works
Qin, C., Hu, Y., Zhou, B., Fernandez-Salas, E., Yang, C.-Y., Liu, L., McEachern, D., Przybranowski, S., Wang, M., Stuckey, J., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00506 · Cited by 281 · see citing works
Exploring Targeted Degradation Strategy for Oncogenic KRASG12C
Zeng, M., Xiong, Y., Safaee, N., Nowak, R. P., Donovan, K. A., Yuan, C. J., Nabet, B., Gero, T. W., Feru, F., Li, L., et al. (2020) · Cell Chemical Biology · doi:10.1016/j.chembiol.2019.12.006 · Cited by 275 · see citing works
Development of dual and selective degraders of cyclin-dependent kinases 4 and 6
Jiang, B., Wang, E. S., Donovan, K. A., Liang, Y., Fischer, E. S., Zhang, T., & Gray, N. S. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201901336 · Cited by 272 · see citing works
Structure‐Based Design of a Macrocyclic PROTAC
Testa, A., Hughes, S. J., Lucas, X., Wright, J. E., & Ciulli, A. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201914396 · Cited by 251 · see citing works
de Wispelaere, M., Du, G., Donovan, K. A., Zhang, T., Eleuteri, N. A., Yuan, J. C., Kalabathula, J., Nowak, R. P., Fischer, E. S., Gray, N. S., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11429-w · Cited by 237 · see citing works
PRosettaC: Rosetta Based Modeling of PROTAC Mediated Ternary Complexes
Zaidman, D., Prilusky, J., & London, N. (2020) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c00589 · Cited by 224 · see citing works
Multiplexed Proteome Dynamics Profiling Reveals Mechanisms Controlling Protein Homeostasis
Savitski, M. M., Zinn, N., Faelth-Savitski, M., Poeckel, D., Gade, S., Becher, I., Muelbaier, M., Wagner, A. J., Strohmer, K., Werner, T., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.030 · Cited by 217 · see citing works
Efficient targeted degradation via reversible and irreversible covalent PROTACs
Gabizon, R., Shraga, A., Gehrtz, P., Livnah, E., Gurwicz, N., Avram, L., Unger, T., Albeck, S., Shulman, Z., & London, N. (2020) · doi:10.26434/chemrxiv.11494398.v1 · Cited by 213 · see citing works
<i>In Silico</i> Modeling of PROTAC-Mediated Ternary Complexes: Validation and Application
Drummond, M. L., & Williams, C. I. (2019) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.8b00872 · Cited by 199 · see citing works
Self-citationPROTAC-Mediated Degradation of Bruton’s Tyrosine Kinase Is Inhibited by Covalent Binding
Tinworth, C. P., Lithgow, H., Dittus, L., Bassi, Z. I., Hughes, S. E., Muelbaier, M., Dai, H., Smith, I. E. D., Kerr, W. J., Burley, G. A., et al. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.8b01094 · Cited by 195 · see citing works
Harnessing the Power of Proteolysis for Targeted Protein Inactivation
Verma, R., Mohl, D., & Deshaies, R. J. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.01.010 · Cited by 185 · see citing works
Assessing Different E3 Ligases for Small Molecule Induced Protein Ubiquitination and Degradation
Ottis, P., Toure, M., Cromm, P. M., Ko, E., Gustafson, J. L., & Crews, C. M. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.7b00485 · Cited by 176 · see citing works
PROTACs– a game-changing technology
Konstantinidou, M., Li, J., Zhang, B., Wang, Z., Shaabani, S., ter Brake, F., Essa, K., & Dömling, A. S. S. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1659242 · Cited by 167 · see citing works
Search strategies and evaluation in protein–protein docking: principles, advances and challenges
Huang, S. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.02.005 · Cited by 164 · see citing works
Developing degraders: principles and perspectives on design and chemical space
Maple, H. J., Clayden, N., Baron, A., Stacey, C., & Felix, R. L. (2019) · MedChemComm · doi:10.1039/c9md00272c · Cited by 159 · see citing works
Rationalizing PROTAC-Mediated Ternary Complex Formation Using Rosetta
Bai, N., Miller, S. A., Andrianov, G. V., Yates, M., Kirubakaran, P., & Karanicolas, J. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c01451 · Cited by 157 · see citing works
Buckley, D. L., & Crews, C. M. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201307761 · Cited by 153 · see citing works
Ottis, P., Palladino, C., Thienger, P., Britschgi, A., Heichinger, C., Berrera, M., Julien-Laferrière, A., Roudnicky, F., Kam‐Thong, T., Bischoff, J. R., et al. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.9b00525 · Cited by 153 · see citing works
Shibata, N., Nagai, K., Morita, Y., Ujikawa, O., Ohoka, N., Hattori, T., Koyama, R., Sano, O., Imaeda, Y., Nara, H., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00168 · Cited by 147 · see citing works
Targeted protein degradation and the enzymology of degraders
Fisher, S. L., & Phillips, A. J. (2018) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2018.05.004 · Cited by 126 · see citing works
Bivalent Ligands for Protein Degradation in Drug Discovery
Scheepstra, M., Hekking, K. F. W., Hijfte, L. V., & Folmer, R. H. A. (2019) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2019.01.006 · Cited by 120 · see citing works
Wang, Z., He, N., Guo, Z., Niu, C., Song, T., Guo, Y., Cao, K., Wang, A., Zhu, J., Zhang, X., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00919 · Cited by 120 · see citing works
Mayor-Ruiz, C., Jaeger, M. G., Bauer, S., Brand, M., Sin, C., Hanzl, A., Mueller, A. C., Menche, J., & Winter, G. E. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.07.013 · Cited by 119 · see citing works
A chemical approach for global protein knockdown from mice to non-human primates
Sun, X., Wang, J., Yao, X., Zheng, W., Mao, Y., Lan, T., Wang, L., Sun, Y., Zhang, X., Zhao, Q., et al. (2019) · Cell Discovery · doi:10.1038/s41421-018-0079-1 · Cited by 118 · see citing works
Development and Characterization of a Wee1 Kinase Degrader
Li, Z., Pinch, B. J., Olson, C. M., Donovan, K. A., Nowak, R. P., Mills, C. E., Scott, D. A., Doctor, Z. M., Eleuteri, N. A., Chung, M., et al. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.10.013 · Cited by 107 · see citing works
Huang, S. (2015) · Drug Discovery Today · doi:10.1016/j.drudis.2015.03.007 · Cited by 106 · see citing works
Bifunctional chemical probes inducing protein–protein interactions
Maniaci, C., & Ciulli, A. (2019) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.07.003 · Cited by 100 · see citing works
Demonstrating In-Cell Target Engagement Using a Pirin Protein Degradation Probe (CCT367766)
Chessum, N. E. A., Sharp, S. Y., Caldwell, J., Pasqua, E., Wilding, B., Colombano, G., Collins, I., Özer, B., Richards, M., Rowlands, M., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01406 · Cited by 90 · see citing works
Zhang, X., Thummuri, D., He, Y., Liu, X., Zhang, P., Zhou, D., & Zheng, G. (2019) · Chemical Communications · doi:10.1039/c9cc07217a · Cited by 86 · see citing works
Hi-JAK-ing the ubiquitin system: The design and physicochemical optimisation of JAK PROTACs
Shah, R. R., Redmond, J. M., Mihut, A., Menon, M. R., Evans, J. P., Murphy, J. A., Bartholomew, M. A., & Coe, D. M. (2020) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2020.115326 · Cited by 75 · see citing works
Monitoring and deciphering protein degradation pathways inside cells
Daniels, D. L., Riching, K. M., & Urh, M. (2018) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2018.12.001 · Cited by 68 · see citing works
Native Mass Spectrometry Can Effectively Predict PROTAC Efficacy
Beveridge, R., Kessler, D., Rumpel, K., Ettmayer, P., Meinhart, A., & Clausen, T. (2020) · ACS Central Science · doi:10.1021/acscentsci.0c00049 · Cited by 67 · see citing works
Unbiasing Scoring Functions: A New Normalization and Rescoring Strategy
Carta, G., Knox, A. J. S., & Lloyd, D. G. (2007) · Journal of Chemical Information and Modeling · doi:10.1021/ci600471m · Cited by 56 · see citing works
Targeted protein degradation mechanisms
Zhang, Y., Loh, C., Chen, J., & Mainolfi, N. (2019) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2019.01.001 · Cited by 45 · see citing works
The size matters? A computational tool to design bivalent ligands
Pérez‐Benito, L., Henry, A., Matsoukas, M., Lopez, L., Pulido, D., Royo, M., Cordomí, A., Tresadern, G., & Pardo, L. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty422 · Cited by 28 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [54](54) Gadd, M. S.; Testa, A.; Lucas, X.; Chan, K. H.; Chen, W.; Lamont, D. J.; Zengerle, M.; Ciulli, A. Structural Basis of PROTAC Cooperative Recognition for Selective Protein Degradation. Nat. Chem. Biol. 2017 , 13 (5), 514 -521. -
Cited by
Sorted by citations
Protein degraders enter the clinic — a new approach to cancer therapy
Chirnomas, D., Hornberger, K. R., & Crews, C. M. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00736-3 · Cited by 658 · see citing works
Chemistries of bifunctional PROTAC degraders
Cao, C., He, M., Wang, L., He, Y., & Rao, Y. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00220e · Cited by 313 · see citing works
PRosettaC: Rosetta Based Modeling of PROTAC Mediated Ternary Complexes
Zaidman, D., Prilusky, J., & London, N. (2020) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c00589 · Cited by 224 · see citing works
Chasing molecular glue degraders: screening approaches
Domostegui, A., Nieto-Barrado, L., Perez-Lopez, C., & Mayor-Ruiz, C. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00197g · Cited by 200 · see citing works
Rationalizing PROTAC-Mediated Ternary Complex Formation Using Rosetta
Bai, N., Miller, S. A., Andrianov, G. V., Yates, M., Kirubakaran, P., & Karanicolas, J. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c01451 · Cited by 157 · see citing works
Integrative Modeling of PROTAC-Mediated Ternary Complexes
Weng, G., Li, D., Kang, Y., & Hou, T. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01576 · Cited by 130 · see citing works
Bai, N., Riching, K. M., Makaju, A., Wu, H., Acker, T. M., Ou, S.-C., Zhang, Y., Shen, X., Bulloch, D. N., Rui, H., et al. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101653 · Cited by 77 · see citing works
Li, W., Zhang, J., Guo, L., & Wang, Q. (2022) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.1c01150 · Cited by 63 · see citing works
Eron, S. J., Huang, H., Agafonov, R. V., Fitzgerald, M. E., Patel, J., Michael, R. E., Lee, T. D., Hart, A. A., Shaulsky, J., Nasveschuk, C. G., et al. (2021) · ACS Chemical Biology · doi:10.1021/acschembio.1c00376 · Cited by 57 · see citing works
Unifying Catalysis Framework to Dissect Proteasomal Degradation Paradigms
Rodriguez-Rivera, F. P., & Levi, S. M. (2021) · ACS Central Science · doi:10.1021/acscentsci.1c00389 · Cited by 30 · see citing works
Dixon, T., MacPherson, D., Mostofian, B., Dauzhenka, T., Lotz, S., McGee, D., Shechter, S., Shrestha, U. R., Wiewiora, R., McDargh, Z. A., et al. (2021) · doi:10.1101/2021.09.26.461830 · Cited by 7 · see citing works
- Authors
- Drummond, M. L., Henry, A., Li, H., & Williams, C. I.
- Affiliations
- Chemical Computing Group , , ,
- University of Cambridge (GB)
- Corresponding author
- Drummond, Michael L.
- Venue
- Journal of Chemical Information and Modeling
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-09-24
- Volume
- 60
- Issue
- 10
- Pages
- 5234-5254
- ISSN
- 1549-9596 (ISSN-L)
- 1549-960X
- OpenAlex
- W3088011183
- Cited by
- 166
- References
- 68
- Citations by year
- 2026: 23 · 2025: 42 · 2024: 34 · 2023: 29 · 2022: 21 · 2021: 16 · 2020: 1
- FWCI
- 5.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Chemical Information and Modeling (publishedVersion, other-oa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- 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
- Keywords
- PROTACs, targeted protein degradation, E3 ubiquitin ligase, protein-protein interaction, protein structure prediction, clustering, PROTAC design
- MeSH terms
- Computer Simulation, Retrospective Studies, Small Molecule Libraries, Proteolysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
