{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T02:01:17Z","timestamp":1787623277307,"version":"build-2736575974"},"reference-count":80,"publisher":"American Chemical Society (ACS)","issue":"15","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation for Higher Education Institutions of Jiangsu Province, China"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Foundation of Jiangsu Province, China"},{"name":"Basic Research Program of Jiangsu","award":["BK20255001"],"award-info":[{"award-number":["BK20255001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Post-translational modifications (PTMs) and somatic mutations are pervasive in cancer, yet their three-dimensional organization and coordinated regulatory mechanisms within protein\u2013protein interactions (PPIs) remain poorly understood. Here we develop ClusTar, a structural framework that systematically identifies spatial clusters of PTMs and mutations within PPIs and links them to protein dynamics and functional regulation. Integrating TCGA genomics, CPTAC proteomics, and structural PPI data across ten cancer types, we identify 3,966 high-confidence PTM\u2013mutation clusters that are enriched in functional residues and frequently overlap with ligand-binding pockets. Dynamics analyses reveal that many clusters are mechanically coupled to PPI interfaces and mediate long-range allosteric communications. In RhoA complexes, glutamine substitutions at acetylated lysine sites (K7Q, K18Q, K104Q and K118Q\/K162Q) have been observed to redistribute key network hubs and rewire allosteric communication pathways among clustered residues. Experimental validation demonstrates that these mutations strengthen protein interactions and promote breast cancer cell migration, highlighting their potential as allosteric hotspots. Together, our results establish a pan-cancer structural atlas of PTM\u2013mutation clusters and highlight allosteric hotspots as potential targets for modulating PPIs.<\/jats:p>","DOI":"10.1021\/acs.jcim.6c01767","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:13:31Z","timestamp":1784304811000},"page":"9408-9428","source":"Crossref","is-referenced-by-count":1,"title":["Pan-Cancer Landscape\nof Spatial PTM and Mutation Clusters\nReveals Allosteric Regulation of Protein\u2013Protein Interactions"],"prefix":"10.1021","volume":"66","author":[{"given":"Dongfang","family":"Luo","sequence":"first","affiliation":[{"name":"Suzhou Medical College of Soochow University , , , ,","place":["Suzhou, Jiangsu, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiani","family":"Zheng","sequence":"additional","affiliation":[{"name":"Suzhou Medical College of Soochow University , , , ,","place":["Suzhou, Jiangsu, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xikun","family":"Du","sequence":"additional","affiliation":[{"name":"Suzhou Medical College of Soochow University , , , ,","place":["Suzhou, Jiangsu, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danni","family":"Xia","sequence":"additional","affiliation":[{"name":"Suzhou Medical College of Soochow University , , ,","place":["Suzhou, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Suzhou Medical College of Soochow University , , ,","place":["Suzhou, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0763-5407","authenticated-orcid":true,"given":"Zhongjie","family":"Liang","sequence":"additional","affiliation":[{"name":"Suzhou Medical College of Soochow University , , , ,","place":["Suzhou, Jiangsu, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"2026081008091252900_cit1","doi-asserted-by":"publisher","first-page":"D554","DOI":"10.1093\/nar\/gkae850","article-title":"PTMD 2.0: an updated database of disease-associated post-translational\nmodifications","volume":"53","author":"Huang","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"2026081008091252900_cit2","doi-asserted-by":"publisher","first-page":"D377","DOI":"10.1093\/nar\/gkae1005","article-title":"dbPTM 2025 update: comprehensive\nintegration of PTMs and proteomic\ndata for advanced insights into cancer research","volume":"53","author":"Chung","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"2026081008091252900_cit3","doi-asserted-by":"publisher","first-page":"3945","DOI":"10.1016\/j.cell.2023.07.013","article-title":"Pan-cancer analysis of post-translational modifications\nreveals shared patterns of protein regulation","volume":"186","author":"Geffen","year":"2023","journal-title":"Cell"},{"key":"2026081008091252900_cit4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2524289123","article-title":"An interpretable molecular\nframework for predicting cancer driver missense mutations","volume":"123","author":"Yang","year":"2026","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026081008091252900_cit5","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1002\/med.21774","article-title":"Drug design targeting\nactive posttranslational modification protein isoforms","volume":"41","author":"Meng","year":"2021","journal-title":"Medicinal research reviews"},{"key":"2026081008091252900_cit6","doi-asserted-by":"publisher","first-page":"D901","DOI":"10.1093\/nar\/gkx973","article-title":"ActiveDriverDB: human disease mutations and genome\nvariation in post-translational modification sites of proteins","volume":"46","author":"Krassowski","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2026081008091252900_cit7","doi-asserted-by":"publisher","first-page":"E5486","DOI":"10.1073\/pnas.1516373112","article-title":"Comprehensive\nassessment of cancer missense mutation clustering in protein structures","volume":"112","author":"Kamburov","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026081008091252900_cit8","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1038\/ng.3586","article-title":"Protein-structure-guided\ndiscovery of functional\nmutations across 19 cancer types","volume":"48","author":"Niu","year":"2016","journal-title":"Nature genetics"},{"key":"2026081008091252900_cit9","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114905","article-title":"Protein structural\ncontext of cancer mutations reveals molecular mechanisms and candidate\ndriver genes","volume":"43","author":"Chillon-Pino","year":"2024","journal-title":"Cell Rep"},{"key":"2026081008091252900_cit10","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1038\/s41467-019-09952-x","article-title":"Conserved\nphosphorylation hotspots\nin eukaryotic protein domain families","volume":"10","author":"Strumillo","year":"2019","journal-title":"Nat.\nCommun."},{"key":"2026081008091252900_cit11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001636","article-title":"The structural\ncontext of posttranslational modifications at a proteome-wide scale","volume":"20","author":"Bludau","year":"2022","journal-title":"PLoS biology"},{"key":"2026081008091252900_cit12","doi-asserted-by":"publisher","first-page":"2313","DOI":"10.1038\/s41467-021-22481-w","article-title":"Spatially interacting\nphosphorylation\nsites and mutations in cancer","volume":"12","author":"Huang","year":"2021","journal-title":"Nat. Commun."},{"key":"2026081008091252900_cit13","doi-asserted-by":"publisher","first-page":"18962","DOI":"10.1073\/pnas.1901156116","article-title":"Leveraging\nprotein dynamics to identify\ncancer mutational hotspots using 3D structures","volume":"116","author":"Kumar","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026081008091252900_cit14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2025.169326","article-title":"Deciphering\nAllosteric Disease Mutations Through Intrinsic Dynamics","volume":"437","author":"Kaskaloglu","year":"2025","journal-title":"J. Mol. Biol."},{"key":"2026081008091252900_cit15","doi-asserted-by":"publisher","first-page":"4164","DOI":"10.1073\/pnas.1715896115","article-title":"Structural dynamics is a determinant\nof the functional significance\nof missense variants","volume":"115","author":"Ponzoni","year":"2018","journal-title":"Proc. Natl. Acad. Sci.\nU.S.A."},{"key":"2026081008091252900_cit16","doi-asserted-by":"publisher","first-page":"e2418100122","DOI":"10.1073\/pnas.2418100122","article-title":"Accurate identification and mechanistic\nevaluation of pathogenic missense variants with Rhapsody-2","volume":"122","author":"Banerjee","year":"2025","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026081008091252900_cit17","doi-asserted-by":"publisher","first-page":"9407","DOI":"10.1038\/s41467-025-64116-4","article-title":"Global comparative\nstructural analysis of responses to protein phosphorylation","volume":"16","author":"Correa Marrero","year":"2025","journal-title":"Nat. Commun."},{"key":"2026081008091252900_cit18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.131180","article-title":"FuncPhos-STR: An integrated deep\nneural network for functional phosphosite\nprediction based on AlphaFold protein structure and dynamics","volume":"266","author":"Zhang","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"2026081008091252900_cit19","doi-asserted-by":"publisher","first-page":"15111","DOI":"10.1021\/acs.jmedchem.1c01076","article-title":"Dynamics of Post-Translational\nModification Inspires Drug Design\nin the Kinase Family","volume":"64","author":"Zhang","year":"2021","journal-title":"Journal of medicinal chemistry"},{"key":"2026081008091252900_cit20","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/s41392-024-02036-3","article-title":"New insights into protein\u2013protein\ninteraction modulators in\ndrug discovery and therapeutic advance","volume":"9","author":"Nada","year":"2024","journal-title":"Signal\nTransduction and Targeted Therapy"},{"key":"2026081008091252900_cit21","doi-asserted-by":"publisher","first-page":"D376","DOI":"10.1093\/nar\/gkad915","article-title":"ASD2023: towards the\nintegrating landscapes of allosteric knowledgebase","volume":"52","author":"He","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"2026081008091252900_cit22","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1021\/acs.jcim.6b00039","article-title":"Motions of Allosteric and Orthosteric\nLigand-Binding Sites in Proteins are Highly Correlated","volume":"56","author":"Ma","year":"2016","journal-title":"J. Chem. Inf. Model."},{"key":"2026081008091252900_cit23","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1021\/acs.jcim.1c01267","article-title":"Uncovering\nthe Dominant Motion Modes of Allosteric Regulation Improves Allosteric\nSite Prediction","volume":"62","author":"Xie","year":"2022","journal-title":"J. Chem. Inf. Model."},{"key":"2026081008091252900_cit24","doi-asserted-by":"publisher","first-page":"W33","DOI":"10.1093\/nar\/gkad279","article-title":"AlloReverse: multiscale understanding among\nhierarchical allosteric\nregulations","volume":"51","author":"Zha","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"2026081008091252900_cit25","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1016\/j.tcb.2006.08.006","article-title":"Rho GTPases\nand actin dynamics in membrane protrusions and vesicle trafficking","volume":"16","author":"Ridley","year":"2006","journal-title":"Trends in cell biology"},{"key":"2026081008091252900_cit26","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/nrm1587","article-title":"GEF means go: turning\non RHO GTPases\nwith guanine nucleotide-exchange factors","volume":"6","author":"Rossman","year":"2005","journal-title":"Nat.\nRev. Mol. Cell Biol."},{"key":"2026081008091252900_cit27","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1042\/BJ20140606","article-title":"The crystal structure of the RhoA\u2013AKAP-Lbc\nDH\u2013PH domain complex","volume":"464","author":"Abdul Azeez","year":"2014","journal-title":"Biochem. J."},{"key":"2026081008091252900_cit28","doi-asserted-by":"publisher","first-page":"33026","DOI":"10.1074\/jbc.M504587200","article-title":"RA-RhoGAP,\nRap-activated Rho GTPase-activating protein implicated in neurite\noutgrowth through Rho","volume":"280","author":"Yamada","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2026081008091252900_cit29","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1161\/01.RES.0000170084.88780.ea","article-title":"Phosphorylation of\nserine 188 protects RhoA from ubiquitin\/proteasome-mediated degradation\nin vascular smooth muscle cells","volume":"96","author":"Rolli-Derkinderen","year":"2005","journal-title":"Circulation\nresearch"},{"key":"2026081008091252900_cit30","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1002\/j.1460-2075.1996.tb00383.x","article-title":"Protein kinase A phosphorylation of RhoA mediates the\nmorphological and functional effects of cyclic AMP in cytotoxic lymphocytes","volume":"15","author":"Lang","year":"1996","journal-title":"EMBO journal"},{"key":"2026081008091252900_cit31","doi-asserted-by":"publisher","first-page":"341a","DOI":"10.1016\/j.bpj.2018.11.1858","article-title":"The mechanism\nof PI3K\u03b1 activation\nat the atomic level","volume":"116","author":"Zhang","year":"2019","journal-title":"Biophys. J."},{"key":"2026081008091252900_cit32","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1073\/pnas.0510857103","article-title":"Cancer-specific\nmutations in PIK3CA\nare oncogenic in vivo","volume":"103","author":"Bader","year":"2006","journal-title":"Proc. Natl. Acad. Sci.\nU. S. A."},{"key":"2026081008091252900_cit33","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1158\/1541-7786.MCR-17-0260","article-title":"Functional impact of chromatin remodeling\ngene mutations and predictive signature for therapeutic response in\nbladder cancer","volume":"16","author":"Duex","year":"2018","journal-title":"Molecular Cancer Research"},{"key":"2026081008091252900_cit34","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1038\/ng.3076","article-title":"Genetic landscape\nof esophageal squamous cell carcinoma","volume":"46","author":"Gao","year":"2014","journal-title":"Nature\ngenetics"},{"key":"2026081008091252900_cit35","doi-asserted-by":"publisher","first-page":"36605","DOI":"10.1074\/jbc.M109.039537","article-title":"Double superhelix model\nof high density lipoprotein","volume":"284","author":"Wu","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2026081008091252900_cit36","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1016\/j.jmb.2007.04.084","article-title":"The crystal\nstructure of the human Mov34 MPN domain reveals a metal-free dimer","volume":"370","author":"Sanches","year":"2007","journal-title":"Journal of molecular biology"},{"key":"2026081008091252900_cit37","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1126\/science.adl2688","article-title":"Reversible male contraception\nby targeted inhibition\nof serine\/threonine kinase 33","volume":"384","author":"Ku","year":"2024","journal-title":"Science"},{"key":"2026081008091252900_cit38","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.molcel.2011.01.013","article-title":"Structural\nbasis for dimerization and activity of human PAPD1, a noncanonical\npoly (A) polymerase","volume":"41","author":"Bai","year":"2011","journal-title":"Molecular cell"},{"key":"2026081008091252900_cit39","doi-asserted-by":"publisher","first-page":"D404","DOI":"10.1093\/nar\/gkad630","article-title":"BioLiP2: an updated\nstructure database for biologically relevant ligand\u2013protein\ninteractions","volume":"52","author":"Zhang","year":"2024","journal-title":"Nucleic acids research"},{"key":"2026081008091252900_cit40","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/1471-2105-10-168","article-title":"Fpocket: an open source\nplatform for ligand pocket detection","volume":"10","author":"Le Guilloux","year":"2009","journal-title":"BMC bioinformatics"},{"key":"2026081008091252900_cit41","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1002\/jcb.30128","article-title":"14\u20133-3\u03b2\nisoform is specifically acetylated at Lys51 during differentiation\nto the osteogenic lineage","volume":"122","author":"Frontini-Lo\u0301pez","year":"2021","journal-title":"Journal of Cellular\nBiochemistry"},{"key":"2026081008091252900_cit42","doi-asserted-by":"publisher","first-page":"10886","DOI":"10.1021\/jacs.4c11102","article-title":"Holdup Multiplex\nAssay for High-Throughput\nMeasurement of Protein\u2013Ligand Affinity Constants Using a Mass\nSpectrometry Readout","volume":"147","author":"Delalande","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"2026081008091252900_cit43","doi-asserted-by":"publisher","first-page":"8454","DOI":"10.1021\/jacs.1c03035","article-title":"Reversible\ncovalent imine-tethering\nfor selective stabilization of 14\u20133-3 hub protein interactions","volume":"143","author":"Cossar","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"2026081008091252900_cit44","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/j.molcel.2011.07.021","article-title":"Liprin-mediated large signaling complex organization revealed by\nthe liprin-\u03b1\/CASK and liprin-\u03b1\/liprin-\u03b2 complex\nstructures","volume":"43","author":"Wei","year":"2011","journal-title":"Molecular cell"},{"key":"2026081008091252900_cit45","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.cell.2008.02.036","article-title":"CASK Functions as\na Mg2+-independent neurexin kinase","volume":"133","author":"Mukherjee","year":"2008","journal-title":"Cell"},{"key":"2026081008091252900_cit46","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1038\/nchembio.1930","article-title":"New IDH1 mutant inhibitors for treatment of acute myeloid\nleukemia","volume":"11","author":"Okoye-Okafor","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"2026081008091252900_cit47","doi-asserted-by":"publisher","first-page":"6647","DOI":"10.1021\/acs.jmedchem.8b00305","article-title":"Novel modes\nof inhibition of wild-type isocitrate dehydrogenase 1 (IDH1): direct\ncovalent modification of His315","volume":"61","author":"Jakob","year":"2018","journal-title":"J. Med. Chem."},{"key":"2026081008091252900_cit48","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.ccell.2018.04.011","article-title":"Biological\nrole and therapeutic potential\nof IDH mutations in cancer","volume":"34","author":"Waitkus","year":"2018","journal-title":"Cancer cell"},{"key":"2026081008091252900_cit49","doi-asserted-by":"publisher","first-page":"4723","DOI":"10.1016\/j.jmb.2016.10.017","article-title":"Structural dynamics\nin Ras and related proteins upon nucleotide switching","volume":"428","author":"Harrison","year":"2016","journal-title":"Journal of molecular biology"},{"key":"2026081008091252900_cit50","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s13073-016-0393-x","article-title":"3D clusters of somatic\nmutations in cancer reveal numerous\nrare mutations as functional targets","volume":"9","author":"Gao","year":"2017","journal-title":"Genome\nmedicine"},{"key":"2026081008091252900_cit51","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1038\/ng.2359","article-title":"Exome sequencing identifies\nrecurrent somatic RAC1 mutations in melanoma","volume":"44","author":"Krauthammer","year":"2012","journal-title":"Nature genetics"},{"key":"2026081008091252900_cit52","doi-asserted-by":"publisher","first-page":"5731","DOI":"10.1158\/1078-0432.CCR-08-0646","article-title":"Frequency and distinctive spectrum of KRAS mutations in never smokers\nwith lung adenocarcinoma","volume":"14","author":"Riely","year":"2008","journal-title":"Clinical cancer research"},{"key":"2026081008091252900_cit53","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1016\/j.jmoldx.2014.06.004","article-title":"Prospective\nenterprise-level molecular genotyping of\na cohort of cancer patients","volume":"16","author":"MacConaill","year":"2014","journal-title":"Journal of Molecular\nDiagnostics"},{"key":"2026081008091252900_cit54","doi-asserted-by":"publisher","first-page":"9265","DOI":"10.1200\/JCO.2005.03.0536","article-title":"Randomized phase II trial of the\nclinical and biological effects of two dose levels of gefitinib in\npatients with recurrent colorectal adenocarcinoma","volume":"23","author":"Rothenberg","year":"2005","journal-title":"Journal of clinical oncology"},{"key":"2026081008091252900_cit55","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1126\/science.aad6204","article-title":"Allele-specific\ninhibitors inactivate mutant KRAS G12C by a trapping mechanism","volume":"351","author":"Lito","year":"2016","journal-title":"Science"},{"key":"2026081008091252900_cit56","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1200\/JCO.2008.20.8397","article-title":"Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab\nin the first-line treatment of metastatic colorectal cancer","volume":"27","author":"Bokemeyer","year":"2009","journal-title":"Journal of clinical oncology"},{"key":"2026081008091252900_cit57","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1016\/j.cellsig.2011.04.001","article-title":"Cdc42 in oncogenic\ntransformation, invasion, and tumorigenesis","volume":"23","author":"Stengel","year":"2011","journal-title":"Cellular signalling"},{"key":"2026081008091252900_cit58","doi-asserted-by":"publisher","first-page":"361","DOI":"10.3390\/cancers17030361","article-title":"RAC1-amplified and RAC1-A159V hotspot-mutated head\nand neck cancer\nsensitive to the Rac inhibitor EHop-016 in vivo: A proof-of-concept\nstudy","volume":"17","author":"Chan","year":"2025","journal-title":"Cancers"},{"key":"2026081008091252900_cit59","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1158\/2159-8290.CD-16-0160","article-title":"Systematic\nfunctional interrogation of rare cancer variants identifies oncogenic\nalleles","volume":"6","author":"Kim","year":"2016","journal-title":"Cancer discovery"},{"key":"2026081008091252900_cit60","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/nbt.3391","article-title":"Identifying recurrent\nmutations in cancer reveals widespread\nlineage diversity and mutational specificity","volume":"34","author":"Chang","year":"2016","journal-title":"Nature biotechnology"},{"key":"2026081008091252900_cit61","doi-asserted-by":"publisher","first-page":"35308","DOI":"10.1074\/jbc.M704426200","article-title":"AKAP13, a RhoA GTPase-specific guanine exchange factor,\nis a novel regulator of TLR2 signaling","volume":"282","author":"Shibolet","year":"2007","journal-title":"J. Biol.\nChem."},{"key":"2026081008091252900_cit62","unstructured":"Hubbard, S.; Thornton, J.\n          NACCESS; Department of Biochemistry and Molecular Biology,\nUniversity College London, 1993."},{"key":"2026081008091252900_cit63","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1158\/2159-8290.CD-13-0219","article-title":"Connecting genomic alterations to\ncancer biology with proteomics: the NCI Clinical Proteomic Tumor Analysis\nConsortium","volume":"3","author":"Ellis","year":"2013","journal-title":"Cancer discovery"},{"key":"2026081008091252900_cit64","doi-asserted-by":"publisher","first-page":"D512","DOI":"10.1093\/nar\/gku1267","article-title":"PhosphoSitePlus, 2014:\nmutations,\nPTMs and recalibrations","volume":"43","author":"Hornbeck","year":"2015","journal-title":"Nucleic acids research"},{"key":"2026081008091252900_cit65","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btac823","article-title":"PTMint\ndatabase of experimentally verified PTM regulation\non protein\u2013protein interaction","volume":"39","author":"Hong","year":"2023","journal-title":"Bioinformatics"},{"key":"2026081008091252900_cit66","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.gpb.2018.06.004","article-title":"PTMD: a database\nof human disease-associated post-translational\nmodifications","volume":"16","author":"Xu","year":"2018","journal-title":"Genomics, proteomics & bioinformatics"},{"key":"2026081008091252900_cit67","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13073-018-0531-8","article-title":"Cancer Genome\nInterpreter annotates\nthe biological and clinical relevance of tumor alterations","volume":"10","author":"Tamborero","year":"2018","journal-title":"Genome medicine"},{"key":"2026081008091252900_cit68","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bau104","article-title":"Kin-Driver: a database of driver mutations in protein\nkinases","volume":"2014","author":"Simonetti","year":"2014","journal-title":"Database"},{"key":"2026081008091252900_cit69","doi-asserted-by":"publisher","first-page":"D941","DOI":"10.1093\/nar\/gky1015","article-title":"COSMIC: the catalogue\nof somatic mutations in cancer","volume":"47","author":"Tate","year":"2019","journal-title":"Nucleic acids\nresearch"},{"key":"2026081008091252900_cit70","doi-asserted-by":"publisher","first-page":"D1265","DOI":"10.1093\/nar\/gkad976","article-title":"DrugBank 6.0: the DrugBank knowledgebase for 2024","volume":"52","author":"Knox","year":"2024","journal-title":"Nucleic acids research"},{"key":"2026081008091252900_cit71","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1093\/bioinformatics\/btr168","article-title":"ProDy: protein dynamics inferred\nfrom theory and experiments","volume":"27","author":"Bakan","year":"2011","journal-title":"Bioinformatics"},{"key":"2026081008091252900_cit72","doi-asserted-by":"publisher","first-page":"3956","DOI":"10.1093\/bioinformatics\/btab496","article-title":"ClustENMD: efficient\nsampling of biomolecular conformational space at atomic resolution","volume":"37","author":"Kaynak","year":"2021","journal-title":"Bioinformatics"},{"key":"2026081008091252900_cit73","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1002\/jcc.20945","article-title":"CHARMM-GUI: a web-based graphical\nuser interface for CHARMM","volume":"29","author":"Jo","year":"2008","journal-title":"Journal of computational\nchemistry"},{"key":"2026081008091252900_cit74","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance\nmolecular simulations through multi-level parallelism from laptops\nto supercomputers","volume":"1","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"2026081008091252900_cit75","doi-asserted-by":"publisher","first-page":"3276","DOI":"10.1093\/bioinformatics\/btr550","article-title":"MDpocket: open-source\ncavity detection and characterization on molecular dynamics trajectories","volume":"27","author":"Schmidtke","year":"2011","journal-title":"Bioinformatics"},{"key":"2026081008091252900_cit76","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1016\/j.csbj.2021.12.044","article-title":"PSNtools for standalone\nand web-based\nstructure network analyses of conformational ensembles","volume":"20","author":"Felline","year":"2022","journal-title":"Computational and Structural Biotechnology Journal"},{"key":"2026081008091252900_cit77","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein data bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic\nacids research"},{"key":"2026081008091252900_cit78","doi-asserted-by":"publisher","first-page":"11255","DOI":"10.1021\/acs.jcim.5c01504","article-title":"Mapping Context-Aware Phosphosite\nRegulation of Protein\u2013Protein Interactions Using Deep Learning\nand Pan-Cancer Proteomics","volume":"65","author":"Cai","year":"2025","journal-title":"J. Chem. Inf. Model."},{"key":"2026081008091252900_cit79","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1002\/wics.147","article-title":"ggplot2","volume":"3","author":"Wickham","year":"2011","journal-title":"Wiley\ninterdisciplinary reviews: computational statistics"},{"key":"2026081008091252900_cit80","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment\nfor integrated models\nof biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome\nresearch"}],"container-title":["Journal of Chemical Information\nand Modeling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jcim.6c01767","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article-pdf\/66\/15\/9408\/66013441\/acs.jcim.6c01767.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article-pdf\/66\/15\/9408\/66013441\/acs.jcim.6c01767.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T12:30:21Z","timestamp":1786365021000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article\/66\/15\/9408\/5214684\/Pan-Cancer-Landscape-of-Spatial-PTM-and-Mutation"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":80,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,7,17]]},"published-print":{"date-parts":[[2026,8,10]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jcim.6c01767","relation":{},"ISSN":["1549-9596","1549-960X"],"issn-type":[{"value":"1549-9596","type":"print"},{"value":"1549-960X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]}}}