{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:53:13Z","timestamp":1791654793635,"version":"4.3.4"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170079"],"award-info":[{"award-number":["32170079"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32200035"],"award-info":[{"award-number":["32200035"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32400235"],"award-info":[{"award-number":["32400235"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong","doi-asserted-by":"publisher","award":["2024A1515012593"],"award-info":[{"award-number":["2024A1515012593"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong","doi-asserted-by":"publisher","award":["2023A1515110175"],"award-info":[{"award-number":["2023A1515110175"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong","doi-asserted-by":"publisher","award":["2024B1111130001"],"award-info":[{"award-number":["2024B1111130001"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong","doi-asserted-by":"publisher","award":["2021QN020100"],"award-info":[{"award-number":["2021QN020100"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Microbial nonribosomal peptides (NRPs) exhibit remarkable structural diversity and are important sources of lead compounds for clinical drug development. The biosynthesis of NRPs relies on nonribosomal peptide synthetases (NRPSs), in which adenylation (A) domains define the core structure by selectively recognizing and activating amino acid substrates. Accurately predicting the substrate specificities of A-domains is thus essential for understanding the core structural and biosynthetic logic of NRPs. Here, we present DeepAden, a two-stage deep learning model. In the first stage, a graph attention network (GAT)-based model localizes 27-residue binding pockets within 6 \u00c5 of bound substrates and converts these into pocket representations. In the second stage, pocket representations are encoded alongside substrate information using pretrained language models and aligned using contrastive learning. We also applied a SHapley Additive exPlanations (SHAP)-guided data augmentation strategy to mitigate class imbalance, particularly focusing on nonproteinogenic substrates. DeepAden achieved competitive performance compared with state-of-the-art tools on a benchmark dataset and facilitated the annotation of two Streptomyces NRPS gene clusters by providing supportive A-domain substrate-specificity predictions. DeepAden provides a practical approach for pocket localization and substrate prediction and may facilitate the discovery and characterization of new NRP natural products. The DeepAden web server is available at https:\/\/deepnp.site\/.<\/jats:p>","DOI":"10.1093\/nar\/gkag656","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T16:09:58Z","timestamp":1783354198000},"source":"Crossref","is-referenced-by-count":2,"title":["DeepAden: an explainable machine learning method for predicting the substrate specificity of nonribosomal peptide synthetases"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7534-8739","authenticated-orcid":false,"given":"Jiaquan","family":"Huang","sequence":"first","affiliation":[{"name":"Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University , Zhuhai, Guangdong 519087 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangjun","family":"Ge","sequence":"additional","affiliation":[{"name":"Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University , Zhuhai, Guangdong 519087 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University , Zhuhai, Guangdong 519087 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6423-4369","authenticated-orcid":false,"given":"Yi","family":"Tian","sequence":"additional","affiliation":[{"name":"Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University , Zhuhai, Guangdong 519087 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University , Zhuhai, Guangdong 519087 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiandi","family":"Gao","sequence":"additional","affiliation":[{"name":"Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University , Zhuhai, Guangdong 519087 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University , Zhuhai, Guangdong 519087 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Meng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research & Natural Products Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203 ,","place":["People\u2019s Republic of China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100049 ,","place":["People\u2019s Republic of China"]},{"name":"Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Zhongshan 528400 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0196-240X","authenticated-orcid":false,"given":"Heqian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University , Zhuhai, Guangdong 519087 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1444-3684","authenticated-orcid":false,"given":"Zhiwei","family":"Qin","sequence":"additional","affiliation":[{"name":"Center for Biological Science and Technology, Advanced Institute of Natural Sciences, Beijing Normal University , Zhuhai, Guangdong 519087 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"2026070707062925500_B1","doi-asserted-by":"publisher","first-page":"3770","DOI":"10.1002\/anie.201609079","article-title":"Nonribosomal peptide synthesis-principles and prospects","volume":"56","author":"S\u00fcssmuth","year":"2017","journal-title":"Angew Chem Int Ed"},{"key":"2026070707062925500_B2","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1146\/annurev.micro.58.030603.123615","article-title":"Biosynthesis of nonribosomal peptides","volume":"58","author":"Finking","year":"2004","journal-title":"Annu Rev Microbiol"},{"key":"2026070707062925500_B3","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1039\/D3NP00064H","article-title":"Structural, biochemical and bioinformatic analyses of nonribosomal peptide synthetase adenylation domains","volume":"41","author":"Heard","year":"2024","journal-title":"Nat Prod Rep"},{"key":"2026070707062925500_B4","doi-asserted-by":"publisher","first-page":"102212","DOI":"10.1016\/j.cbpa.2022.102212","article-title":"Recent advances in the structural analysis of adenylation domains in natural product biosynthesis","volume":"71","author":"Miyanaga","year":"2022","journal-title":"Curr Opin Chem Biol"},{"key":"2026070707062925500_B5","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1039\/C8NP00036K","article-title":"Structural, functional and evolutionary perspectives on effective re-engineering of non-ribosomal peptide synthetase assembly lines","volume":"35","author":"Brown","year":"2018","journal-title":"Nat Prod Rep"},{"key":"2026070707062925500_B6","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1007\/s10295-018-2084-7","article-title":"Structural basis of the nonribosomal codes for nonproteinogenic amino acid selective adenylation enzymes in the biosynthesis of natural products","volume":"46","author":"Kudo","year":"2019","journal-title":"J Ind Microbiol Biotechnol"},{"key":"2026070707062925500_B7","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/S1074-5521(99)80082-9","article-title":"The specificity-conferring code of adenylation domains in nonribosomal peptide synthetases","volume":"6","author":"Stachelhaus","year":"1999","journal-title":"Chem Biol"},{"key":"2026070707062925500_B8","doi-asserted-by":"publisher","first-page":"5799","DOI":"10.1093\/nar\/gki885","article-title":"Specificity prediction of adenylation domains in nonribosomal peptide synthetases (NRPS) using transductive support vector machines (TSVMs)","volume":"33","author":"Rausch","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2026070707062925500_B9","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/S0959-440X(96)80056-X","article-title":"Hidden Markov models","volume":"6","author":"Eddy","year":"1996","journal-title":"Curr Opin Struct Biol"},{"key":"2026070707062925500_B10","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1109\/5254.708428","article-title":"Support vector machines","volume":"13","author":"Hearst","year":"1998","journal-title":"IEEE Intell Syst Their Appl"},{"key":"2026070707062925500_B11","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Machine Learning"},{"key":"2026070707062925500_B12","doi-asserted-by":"publisher","first-page":"W362","DOI":"10.1093\/nar\/gkr323","article-title":"NRPSpredictor2\u2013a web server for predicting NRPS adenylation domain specificity","volume":"39","author":"R\u00f6ttig","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"2026070707062925500_B13","doi-asserted-by":"publisher","first-page":"3202","DOI":"10.1093\/bioinformatics\/btx400","article-title":"SANDPUMA: ensemble predictions of nonribosomal peptide chemistry reveal biosynthetic diversity across actinobacteria","volume":"33","author":"Chevrette","year":"2017","journal-title":"Bioinformatics"},{"key":"2026070707062925500_B14","doi-asserted-by":"publisher","first-page":"i40","DOI":"10.1093\/bioinformatics\/btad235","article-title":"AdenPredictor: accurate prediction of the adenylation domain specificity of nonribosomal peptide biosynthetic gene clusters in microbial genomes","volume":"39","author":"Mongia","year":"2023","journal-title":"Bioinformatics"},{"key":"2026070707062925500_B15","doi-asserted-by":"publisher","first-page":"2315","DOI":"10.1021\/jacsau.5c01636","article-title":"PARAS: high-accuracy machine learning of substrate specificities in nonribosomal peptide synthetases","volume":"6","author":"Terlouw","year":"2026","journal-title":"JACS Au"},{"key":"2026070707062925500_B16","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/978-94-024-1069-3_11","article-title":"Advances in computational methods for transmembrane protein structure prediction","volume-title":"From Protein Structure to Function with Bioinformatics","author":"Nilmeier","year":"2017"},{"key":"2026070707062925500_B17","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.bbapap.2016.11.008","article-title":"Understand protein functions by comparing the similarity of local structural environments","volume":"1865","author":"Chen","year":"2017","journal-title":"Biochim Biophys Acta Proteins Proteom"},{"key":"2026070707062925500_B18","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41580-021-00407-0","article-title":"A guide to machine learning for biologists","volume":"23","author":"Greener","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026070707062925500_B19","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"2026070707062925500_B20","doi-asserted-by":"publisher","first-page":"138272","DOI":"10.1016\/j.ijbiomac.2024.138272","article-title":"An explainable few-shot learning model for the directed evolution of antimicrobial peptides","volume":"285","author":"Gao","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"2026070707062925500_B21","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1126\/science.ade2574","article-title":"Evolutionary-scale prediction of atomic-level protein structure with a language model","volume":"379","author":"Lin","year":"2023","journal-title":"Science"},{"key":"2026070707062925500_B22","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1038\/s42256-022-00580-7","article-title":"Large-scale chemical language representations capture molecular structure and properties","volume":"4","author":"Ross","year":"2022","journal-title":"Nat Mach Intell"},{"key":"2026070707062925500_B23","doi-asserted-by":"publisher","first-page":"5105","DOI":"10.1021\/acsomega.4c11266","article-title":"MultiT2: a tool connecting the multimodal data for bacterial aromatic polyketide natural products","volume":"10","author":"Ge","year":"2025","journal-title":"Acs Omega"},{"key":"2026070707062925500_B24","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1039\/D3DD00107E","article-title":"A deep learning model for type II polyketide natural product prediction without sequence alignment","volume":"2","author":"Huang","year":"2023","journal-title":"Digital Discovery"},{"key":"2026070707062925500_B25","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/s42256-024-00847-1","article-title":"Physicochemical graph neural network for learning protein\u2013ligand interaction fingerprints from sequence data","volume":"6","author":"Koh","year":"2024","journal-title":"Nat Mach Intell"},{"key":"2026070707062925500_B26","doi-asserted-by":"publisher","first-page":"e2220778120","DOI":"10.1073\/pnas.2220778120","article-title":"Contrastive learning in protein language space predicts interactions between drugs and protein targets","volume":"120","author":"Singh","year":"2023","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026070707062925500_B27","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/978-3-031-20044-1_17","article-title":"Few-shot classification with contrastive learning","volume-title":"Computer Vision \u2013 ECCV 2022","author":"Yang","year":"2022"},{"key":"2026070707062925500_B28","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/s41576-022-00532-2","article-title":"Obtaining genetics insights from deep learning via explainable artificial intelligence","volume":"24","author":"Novakovsky","year":"2023","journal-title":"Nat Rev Genet"},{"key":"2026070707062925500_B29","doi-asserted-by":"publisher","article-title":"Consistent individualized feature attribution for tree ensembles","author":"Lundberg","DOI":"10.48550\/arXiv.1802.03888"},{"key":"2026070707062925500_B30","doi-asserted-by":"publisher","first-page":"e1009736","DOI":"10.1371\/journal.pcbi.1009736","article-title":"Positional SHAP (PoSHAP) for interpretation of machine learning models trained from biological sequences","volume":"18","author":"Dickinson","year":"2022","journal-title":"PLoS Comput Biol"},{"key":"2026070707062925500_B31","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1109\/CVPR.2016.90","article-title":"Deep residual learning for image recognition","volume-title":"Proceedings of the 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR)","author":"He","year":"2016"},{"key":"2026070707062925500_B32","first-page":"4768","article-title":"A unified approach to interpreting model predictions","volume":"30","author":"Lundberg","year":"2017","journal-title":"Adv Neural Inf Process Syst"},{"key":"2026070707062925500_B33","doi-asserted-by":"crossref","first-page":"D678","DOI":"10.1093\/nar\/gkae1115","article-title":"MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration","volume":"53","author":"Zdouc","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"2026070707062925500_B34","doi-asserted-by":"publisher","first-page":"D603","DOI":"10.1093\/nar\/gkac1049","article-title":"MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters","volume":"51","author":"Terlouw","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2026070707062925500_B35","doi-asserted-by":"publisher","first-page":"32662","DOI":"10.1021\/jacs.5c08076","article-title":"NRPStransformer, an accurate adenylation domain specificity prediction algorithm for genome mining of nonribosomal peptides","volume":"147","author":"Zhang","year":"2025","journal-title":"J Am Chem Soc"},{"key":"2026070707062925500_B36","doi-asserted-by":"publisher","first-page":"3150","DOI":"10.1093\/bioinformatics\/bts565","article-title":"CD-HIT: accelerated for clustering the next-generation sequencing data","volume":"28","author":"Fu","year":"2012","journal-title":"Bioinformatics"},{"key":"2026070707062925500_B37","doi-asserted-by":"publisher","first-page":"D785","DOI":"10.1093\/nar\/gkab776","article-title":"GTDB: an ongoing census of bacterial and archaeal diversity through a phylogenetically consistent, rank normalized and complete genome-based taxonomy","volume":"50","author":"Parks","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2026070707062925500_B38","doi-asserted-by":"publisher","first-page":"W46","DOI":"10.1093\/nar\/gkad344","article-title":"antiSMASH 7.0: new and improved predictions for detection, regulation, chemical structures and visualisation","volume":"51","author":"Blin","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2026070707062925500_B39","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/s41592-021-01101-x","article-title":"Sensitive protein alignments at tree-of-life scale using DIAMOND","volume":"18","author":"Buchfink","year":"2021","journal-title":"Nat Methods"},{"key":"2026070707062925500_B40","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s41587-023-01773-0","article-title":"Fast and accurate protein structure search with Foldseek","volume":"42","author":"van\u00a0Kempen","year":"2024","journal-title":"Nat Biotechnol"},{"key":"2026070707062925500_B41","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1126\/science.ads6733","article-title":"Multiple protein structure alignment at scale with FoldMason","volume":"391","author":"Gilchrist","year":"2026","journal-title":"Science"},{"key":"2026070707062925500_B42","doi-asserted-by":"publisher","article-title":"Decoupled weight decay regularization","author":"Loshchilov","DOI":"10.48550\/arXiv.1711.05101"},{"key":"2026070707062925500_B43","first-page":"1026","article-title":"Delving deep into rectifiers: surpassing human-level performance on imageNet classification","volume-title":"Proceedings of the IEEE International Conference on Computer Vision (ICCV)","author":"He","year":"2015"},{"key":"2026070707062925500_B44","first-page":"3","article-title":"LoRA: low-rank adaptation of large language models","volume":"1","author":"Hu","year":"2022","journal-title":"ICLR"},{"key":"2026070707062925500_B45","doi-asserted-by":"publisher","first-page":"3059","DOI":"10.1093\/nar\/gkf436","article-title":"MAFFT: a novel method for rapid multiple sequence alignment based on fast fourier transform","volume":"30","author":"Katoh","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"2026070707062925500_B46","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1093\/molbev\/msu300","article-title":"IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies","volume":"32","author":"Nguyen","year":"2015","journal-title":"Mol Biol Evol"},{"key":"2026070707062925500_B47","doi-asserted-by":"publisher","first-page":"W78","DOI":"10.1093\/nar\/gkae268","article-title":"Interactive Tree of Life (iTOL) v6: recent updates to the phylogenetic tree display and annotation tool","volume":"52","author":"Letunic","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"2026070707062925500_B48","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/BF01908075","article-title":"Comparing partitions","volume":"2","author":"Hubert","year":"1985","journal-title":"J Classification"},{"key":"2026070707062925500_B49","doi-asserted-by":"publisher","article-title":"Deep learning using rectified linear units (ReLU)","author":"Agarap","DOI":"10.48550\/arXiv.1803.08375"},{"key":"2026070707062925500_B50","doi-asserted-by":"publisher","first-page":"eads9530","DOI":"10.1126\/science.ads9530","article-title":"Deep contrastive learning enables genome-wide virtual screening","volume":"391","author":"Jia","year":"2026","journal-title":"Science"},{"key":"2026070707062925500_B51","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/978-1-4419-8339-8_13","article-title":"Remarks on some nonparametric estimates of a density function","volume-title":"Selected Works of Murray Rosenblatt","author":"Davis","year":"2011"},{"key":"2026070707062925500_B52","doi-asserted-by":"crossref","first-page":"31373","DOI":"10.1021\/acs.jafc.5c10698","article-title":"Genomic and metabolic profiling of the endophytic Streptomyces hygroscopicus OsiSh-2 for protective bacterial chemistry","volume":"73","author":"Wu","year":"2025","journal-title":"J Agric Food Chem"},{"key":"2026070707062925500_B53","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/nbt.3597","article-title":"Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking","volume":"34","author":"Wang","year":"2016","journal-title":"Nat Biotechnol"},{"key":"2026070707062925500_B54","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res"},{"key":"2026070707062925500_B55","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/cbic.200500301","article-title":"Nonribosomal peptide synthesis in schizosaccharomyces pombe and the architectures of ferrichrome-type siderophore synthetases in fungi","volume":"7","author":"Schwecke","year":"2006","journal-title":"ChemBioChem"},{"key":"2026070707062925500_B56","doi-asserted-by":"publisher","first-page":"2415","DOI":"10.1074\/jbc.M109.071324","article-title":"Structure of a eukaryotic nonribosomal peptide synthetase adenylation domain that activates a large hydroxamate amino acid in siderophore biosynthesis","volume":"285","author":"Lee","year":"2010","journal-title":"J Biol Chem"},{"key":"2026070707062925500_B57","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/S0022-2836(83)80079-5","article-title":"Ion-pairs in proteins","volume":"168","author":"Barlow","year":"1983","journal-title":"J Mol Biol"},{"key":"2026070707062925500_B58","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1006\/jmbi.1994.1334","article-title":"Satisfying hydrogen bonding potential in proteins","volume":"238","author":"McDonald","year":"1994","journal-title":"J Mol Biol"},{"key":"2026070707062925500_B59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0022-2836(76)90191-1","article-title":"The nature of the accessible and buried surfaces in proteins","volume":"105","author":"Chothia","year":"1976","journal-title":"J Mol Biol"},{"key":"2026070707062925500_B60","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1021\/acs.jnatprod.1c00837","article-title":"Nyuzenamide C, an antiangiogenic epoxy cinnamic acid-containing bicyclic peptide from a riverine Streptomyces sp","volume":"85","author":"An","year":"2022","journal-title":"J Nat Prod"},{"key":"2026070707062925500_B61","doi-asserted-by":"publisher","first-page":"27473","DOI":"10.1021\/acsomega.5c03067","article-title":"Discovery and biosynthesis of nyuzenamides D and E by genome mining in Streptomyces hygroscopicus","volume":"10","author":"Lum","year":"2025","journal-title":"Acs Omega"},{"key":"2026070707062925500_B62","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1021\/acs.orglett.1c00210","article-title":"Nyuzenamides A and B: bicyclic peptides with antifungal and cytotoxic activity from a marine-derived Streptomyces sp","volume":"23","author":"Karim","year":"2021","journal-title":"Org Lett"},{"key":"2026070707062925500_B63","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1021\/acs.jcim.3c01841","article-title":"Machine learning for sequence and structure-based protein-ligand interaction prediction","volume":"64","author":"Zhang","year":"2024","journal-title":"J Chem Inf Model"},{"key":"2026070707062925500_B64","doi-asserted-by":"publisher","first-page":"4131","DOI":"10.1021\/acs.jcim.9b00628","article-title":"Graph convolutional neural networks for predicting drug-target interactions","volume":"59","author":"Torng","year":"2019","journal-title":"J Chem Inf Model"},{"key":"2026070707062925500_B65","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/nrd1129","article-title":"Implications of protein flexibility for drug discovery","volume":"2","author":"Teague","year":"2003","journal-title":"Nat Rev Drug Discov"},{"key":"2026070707062925500_B66","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.1021\/acs.biochem.4c00770","article-title":"Teicoplanin nonribosomal peptide synthetase is unable to incorporate alpha-ketoacid building blocks","volume":"64","author":"Ratnayake","year":"2025","journal-title":"Biochemistry"},{"key":"2026070707062925500_B67","first-page":"98645","article-title":"Structure language models for protein conformation generation","volume-title":"International Conference on Learning Representations","author":"Lu","year":"2025"},{"key":"2026070707062925500_B68","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/s42256-023-00775-6","article-title":"Generation of 3D molecules in pockets via a language model","volume":"6","author":"Feng","year":"2024","journal-title":"Nat Mach Intell"},{"key":"2026070707062925500_B69","doi-asserted-by":"publisher","first-page":"6746","DOI":"10.1021\/jo400708u","article-title":"Surugamides A\u2013E, cyclic octapeptides with four d-amino acid residues, from a marine streptomyces sp.: lC\u2013MS-aided inspection of partial hydrolysates for the distinction of d- and l-amino acid residues in the sequence","volume":"78","author":"Takada","year":"2013","journal-title":"J Org Chem"},{"key":"2026070707062925500_B70","first-page":"5120","article-title":"Wollamides: antimycobacterial cyclic hexapeptides from an Australian soil streptomyces","volume":"16","author":"Khalil","year":"2014","journal-title":"Opt Lett"},{"key":"2026070707062925500_B71","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1021\/acs.jnatprod.5b00009","article-title":"Identification of the biosynthetic gene cluster for the anti-infective desotamides and production of a new analogue in a heterologous host","volume":"78","author":"Li","year":"2015","journal-title":"J Nat Prod"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/54\/13\/gkag656\/68702431\/gkag656.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/54\/13\/gkag656\/68702431\/gkag656.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:07:01Z","timestamp":1783422421000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/doi\/10.1093\/nar\/gkag656\/8725493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":71,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2026,7,3]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkag656","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7,22]]},"published":{"date-parts":[[2026,7,3]]},"article-number":"gkag656"}}