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DrugDomain 2.0: Comprehensive database of protein domains-ligands/drugs interactions across the whole Protein Data Bank
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Abstract
Proteins carry out essential cellular functions - signaling, metabolism, transport - through the specific interaction of small molecules and drugs within their three-dimensional structural domains. Protein domains are conserved folding units that, when combined, drive evolutionary progress. The Evolutionary Classification Of protein Domains (ECOD) places domains into a hierarchy explicitly built around distant evolutionary relationships, enabling the detection of remote homologs across the proteomes. Yet no single resource has systematically mapped domain-ligand interactions at the structural level. To fill this gap, we introduce DrugDomain v2.0, an updated comprehensive resource, that extends earlier releases by linking evolutionary domain classifications (ECOD) to ligand binding events across the entire Protein Data Bank. We also leverage AI-driven predictions from AlphaFold to extend domain-ligand annotations to human drug targets lacking experimental structures. DrugDomain v2.0 catalogs interactions with over 37,000 PDB ligands and 7,560 DrugBank molecules, integrates more than 6,000 small-molecule-associated post-translational modifications, and provides context for 14,000+ PTM-modified human protein models featuring docked ligands. The database encompasses 43,023 unique UniProt accessions and 174,545 PDB structures. The DrugDomain data is available online: https://drugdomain.cs.ucf.edu/ and https://github.com/kirmedvedev/DrugDomain.
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Accurate structure prediction of biomolecular interactions with AlphaFold 3
Abramson, J., Adler, J., Dunger, J., Evans, R., Green, T., Pritzel, A., Ronneberger, O., Willmore, L., Ballard, A. J., Bambrick, J., et al. (2024) · Nature · doi:10.1038/s41586-024-07487-w · Cited by 15,861 · cited 4×
“AlphaFold (AF) has revolutionized structural biology by demonstrating atomic-level precision in protein structure prediction and becoming an indispensable tool in the field [7].”
InfluentialVaradi, M., Bertoni, D., Magana, P., Paramval, U., Pidruchna, I., Radhakrishnan, M., Tsenkov, M., Nair, S., Mirdita, M., Yeo, J., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkad1011 · Cited by 2,052 · cited 1×
“Recently, The Encyclopedia of Domains (TED) [9] was released - a comprehensive resource for the identification and classification of protein domains within the AlphaFold Database [10].”
A structural biology community assessment of AlphaFold2 applications
Akdel, M., Pires, D. E. V., Pardo, E. P., Jänes, J., Zalevsky, A. O., Mészáros, B., Bryant, P., Good, L. L., Laskowski, R. A., Pozzati, G., et al. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00849-w · Cited by 675
HIV-1 assembly, release and maturation
Freed, E. O. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3490 · Cited by 654
Structural basis of HIV-1 maturation inhibitor binding and activity
Sarkar, S., Zadrozny, K. K., Zadorozhnyi, R., Russell, R. W., Quinn, C. M., Kleinpeter, A., Ablan, S., Meshkin, H., Perilla, J. R., Freed, E. O., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36569-y · Cited by 28
Flagged first, then by citations
Research works printed but not linked: 47
- 10.1006/jsbi.2001.4335 · DOI
- 10.1016/j.str.2006.11.009 · DOI
- 10.1093/nar/gkz1064 · DOI
- Waman V.P., Bordin N., Alcraft R., Vickerstaff R., Rauer C., Chan Q. et al: CATH 2024: CATH-AlphaFlow doubles the number of structures in CATH and reveals nearly 200 new folds. J Mol Biol 2024; 436: 168551. · DOI
- 10.1093/nar/gkae1029 · DOI
- 10.1371/journal.pcbi.1011586 · DOI · Paper page
- Schaeffer R.D., Zhang J., Kinch L.N., Pei J., Cong Q. and Grishin N.V.: Classification of domains in predicted structures of the human proteome. Proc Natl Acad Sci USA 2023; 120: e2214069120. · DOI
- 10.1126/science.adq4946 · DOI · Paper page
- Medvedev K.E., Schaeffer R.D., Chen K.S. and Grishin N.V.: Pan-cancer structurome reveals overrepresentation of beta sandwiches and underrepresentation of alpha helical domains. Sci Rep 2023; 13: 11988. · DOI
- Medvedev K.E., Schaeffer R.D. and Grishin N.V.: DrugDomain: the evolutionary context of drugs and small molecules bound to domains. Protein Sci 2024; 33: e5116. · DOI · Paper page
- Medvedev K.E., Schaeffer R.D. and Grishin N.V.: Leveraging AI to explore structural contexts of post-translational modifications in drug binding. J Chemin 2025; 17: 67. · DOI
- 10.1093/nar/28.1.235 · DOI · Paper page
- Westbrook J.D., Shao C., Feng Z., Zhuravleva M., Velankar S. and Young J.: The chemical component dictionary: complete descriptions of constituent molecules in experimentally determined 3D macromolecules in the protein data bank. Bioinformatics 2015; 31: 1274. · DOI
- Piehl D.W., Vallat B., Truong I., Morsy H., Bhatt R., Blaumann S. et al: rcsb-api: python toolkit for streamlining access to RCSB protein data bank APIs. J Mol Biol 2025; 437: 168970. · DOI
- 10.1093/nar/gkad976 · DOI
- Kim S., Chen J., Cheng T., Gindulyte A., He J., He S. et al: PubChem 2025 update. Nucleic Acids Res 2025; 53: D1516. · DOI
- 10.1093/nar/gkad1004 · DOI
- Liu T., Hwang L., Burley S.K., Nitsche C.I., Southan C., Walters W.P. et al: BindingDB in 2024: a FAIR knowledgebase of protein-small molecule binding data. Nucleic Acids Res 2025; 53: D1633. · DOI
- Djoumbou Feunang Y., Eisner R., Knox C., Chepelev L., Hastings J., Owen G. et al: ClassyFire: automated chemical classification with a comprehensive, computable taxonomy. J Chemin 2016; 8: 61. · DOI
- 10.1021/ci200227u · DOI
- 10.1093/bioinformatics/btp163 · DOI · Paper page
- 10.1038/s41592-022-01685-y · DOI · Paper page
- 10.1126/science.adl2528 · DOI · Paper page
- Discovery C., Boitreaud J., Dent J., McPartlon M., Meier J., Reis V. et al: Chai-1: decoding the molecular interactions of life. bioRxiv2024 2024; . 10.10.615955..
- 10.1093/nar/gkac1052 · DOI · Paper page
- The PyMOL Molecular Graphics System : Version 3.0 Schrödinger. : LLC. Accessed January 2024.
- 10.1155/2017/9351507 · DOI
- Magne F., Gotteland M., Gauthier L., Zazueta A., Pesoa S., Navarrete P. et al: The Firmicutes/Bacteroidetes ratio: a relevant marker of gut dysbiosis in obese patients?. Nutrients 2020; 12. · DOI · Paper page
- 10.1038/4441022a · DOI · Paper page
- Procopio R.E., Silva I.R., Martins M.K., Azevedo J.L. and Araujo J.M.: Antibiotics produced by streptomyces. Braz J Infect Dis 2012; 16: 466. · DOI
- Luque C., Cepero A., Perazzoli G., Mesas C., Quinonero F., Cabeza L. et al: In vitro efficacy of extracts and isolated bioactive compounds from ascomycota fungi in the treatment of colorectal cancer: a systematic review. Pharm (Basel) 2022; 16.
- 10.1371/journal.pcbi.1007569 · DOI
- 10.1016/j.jmb.2020.166788 · DOI
- 10.1042/BCJ20220217 · DOI
- Medvedev K.E., Schaeffer R.D., Pei J. and Grishin N.V.: Pathogenic mutation hotspots in protein kinase domain structure. Protein Sci 2023; 32: e4750. · DOI
- Zapf C.W., Bloom J.D., McBean J.L., Dushin R.G., Nittoli T., Otteng M. et al: Macrocyclic lactams as potent Hsp90 inhibitors with excellent tumor exposure and extended biomarker activity. Bioorg Med Chem Lett 2011; 21: 3411. · DOI
- Grundy S.M. and Stone N.J.: 2018 American heart Association/American college of cardiology multisociety guideline on the management of blood cholesterol: primary prevention. JAMA Cardiol 2019; 4: 488. · DOI
- 10.1038/35101544 · DOI
- 10.1126/scitranslmed.abg7859 · DOI
- Kruger F.A., Rostom R. and Overington J.P.: Mapping small molecule binding data to structural domains. BMC Bioinforma 13 Suppl 2012; 17: S11. · DOI
- Li M., Li Y., Lu Y., Li J., Lu X., Ren Y. et al: Molecular basis of Mg(2+) permeation through the human mitochondrial Mrs2 channel. Nat Commun 2023; 14: 4713. · DOI
- Auwercx J., Rybarczyk P., Kischel P., Dhennin-Duthille I., Chatelain D., Sevestre H. et al: Mg(2+) transporters in digestive cancers. Nutrients 2021; 13. · DOI
- 10.1038/s41594-024-01432-1 · DOI
- Noda N.N., Satoo K., Fujioka Y., Kumeta H., Ogura K., Nakatogawa H. et al: Structural basis of Atg8 activation by a homodimeric E1, Atg7. Mol Cell 2011; 44: 462. · DOI
- Campanello G.C., Ruetz M., Dodge G.J., Gouda H., Gupta A., Twahir U.T. et al: Sacrificial Cobalt-Carbon bond homolysis in coenzyme B(12) as a cofactor conservation strategy. J Am Chem Soc 2018; 140: 13205. · DOI
- 10.1038/s41586-018-0680-3 · DOI · Paper page
- Mittelstadt G., Jiao W., Livingstone E.K., Moggre G.J., Nazmi A.R. and Parker E.J.: A dimeric catalytic core relates the short and long forms of ATP-phosphoribosyltransferase. Biochem J 2018; 475: 247. · DOI
Metadata
- Authors
- Medvedev, K. E., Schaeffer, R. D., & Grishin, N. V.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Medvedev, Kirill E.
- Venue
- Computational and Structural Biotechnology Journal
- Published
- 2025-01-01
- Volume
- 27
- Pages
- 4040-4047
- ISSN
- 2001-0370 (ISSN-L)
- PMC
- PMC12475577
- OpenAlex
- W4414625508
- Cited by
- 1
- References
- 5
- Citations by year
- 2026: 1
- FWCI
- 0.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Computational and Structural Biotechnology Journal (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of General Medical Sciences (GM127390, GM147367)
- Welch Foundation (I-1505)
- University of Central Florida
- National Institutes of Health
- National Science Foundation (DBI 2224128)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Keywords
- protein domains, drug binding, Protein Data Bank, ECOD, AlphaFold, post-translational modification, therapeutic target, protein-ligand docking
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