{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:31:21Z","timestamp":1787671881462,"version":"build-2736575974"},"reference-count":86,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004686","name":"King Faisal University","doi-asserted-by":"publisher","award":["KFU260968"],"award-info":[{"award-number":["KFU260968"]}],"id":[{"id":"10.13039\/501100004686","id-type":"DOI","asserted-by":"publisher"}]},{"award":["KFU260968"],"award-info":[{"award-number":["KFU260968"]}],"id":[{"id":"https:\/\/ror.org\/00dn43547","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Wheat (Triticum aestivum), a key global crop, faces rising drought stress that limits root growth and water uptake. Root meristem growth factors (RGFs) are small peptides that regulate root stem cell maintenance, meristem activity, and lateral root formation in model plants, yet the RGF gene family remains unexplored in wheat. Here, we performed a comprehensive genome-wide analysis of the TaRGF gene family, identifying 15 genes distributed across the A, B, and D subgenomes and classified into five homeologous groups (TaRGF1\u2013TaRGF5), predominantly located on chromosomes 2 and 6. All TaRGFs contained a characteristic RGF motif, with dibasic cleavage sites and Asp\u2013Tyr motifs indicating conserved maturation mechanisms. Based on the phylogenetic analysis, the TaRGF5 homeologs showed the highest similarity to Arabidopsis thaliana RGF5. Tested RNA-seq data revealed predominantly root-enriched expression for all TaRGF genes, with TaRGF5 exhibiting the most root-preferential and downregulation under drought stress. Quantitative real-time PCR (qRT-PCR) confirmed that drought stress suppressed the expression of TaRGF5A, TaRGF5B, and TaRGF5D in roots of wheat cultivar Sids-13 across all time points, unlike the higher accumulation seen in controls. Promoter analysis predicted a unique BES1 transcription factor binding site exclusively in TaRGF5B, linking brassinosteroid signaling to peptide-mediated root regulation. Structural modeling and molecular docking predicted an interaction between wheat TaRGF5 homeologs and root growth factor-insensitive receptor kinase (TaRGI3), characterized by conserved sulfotyrosine-mediated binding and favorable interaction energetics. Based on this characterization of the wheat RGF gene family, particularly the potential role of TaRGF5 in root development and drought-adaptation signaling, we propose targeting this gene for functional analysis to improve wheat resilience under water-limited conditions.<\/jats:p>","DOI":"10.3390\/ijms27177616","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:01:07Z","timestamp":1787670067000},"page":"7616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genome-Wide Analysis of Triticum aestivum Root Meristem Growth Factor (RGF) Gene Family Highlights TaRGF5 as a Putative Component of Root-Associated Signaling"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2714-2327","authenticated-orcid":false,"given":"Hala B.","family":"Khalil","sequence":"first","affiliation":[{"name":"Biological Sciences Department, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7133-5611","authenticated-orcid":false,"given":"Haidar A.","family":"Alsahoud","sequence":"additional","affiliation":[{"name":"Biological Sciences Department, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman Darwish","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Genetics Department, Faculty of Agriculture, Ain Shams University, 68 Hadayek Shoubra, Cairo 11241, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatimah A.","family":"Alhassan","sequence":"additional","affiliation":[{"name":"Biological Sciences Department, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norah","family":"Al-helal","sequence":"additional","affiliation":[{"name":"Al-Anjal Private Schools, Al-Ahsa 36361, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2937-4025","authenticated-orcid":false,"given":"Shinya","family":"Ikeno","sequence":"additional","affiliation":[{"name":"Department of Biological Functions and Engineering, Graduate School of Life Science and System Engineering, Kyushu Institute of Technology, 2-4 Hibikino, Wakamatsu Ward, Kitakyushu 808-0196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","unstructured":"FAO (Food and Agriculture Organization of the United Nations) (2017). The Future of Food and Agriculture: Trends and Challenges, Food and Agriculture Organization of the United Nations."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s11103-025-01569-7","article-title":"Enhancing wheat resilience: Biotechnological advances in combating heat stress and environmental challenges","volume":"115","author":"Arif","year":"2025","journal-title":"Plant Mol. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2296094","DOI":"10.1080\/23311932.2023.2296094","article-title":"Drought stress effect, tolerance, and management in wheat\u2014A review","volume":"10","author":"Nyaupane","year":"2024","journal-title":"Cogent Food Agric."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zayed, M.A., and Khalil, H.B. (2023). Plant Cell During Cold Stress: Sensing, Signaling, and Regulations. Crop Sustainability and Intellectual Property Rights, Apple Academic Press.","DOI":"10.1201\/9781003383024-12"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1023\/A:1012455112853","article-title":"Effects of water deficit during germination of wheat seeds","volume":"44","author":"Miazek","year":"2001","journal-title":"Biol. Plant."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5117","DOI":"10.1093\/jxb\/erab124","article-title":"Recognizing the hidden half in wheat: Root system attributes associated with drought tolerance","volume":"72","author":"Li","year":"2021","journal-title":"J. Exp. Bot."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"941","DOI":"10.21475\/ajcs.17.11.08.pne351","article-title":"Wheat phenology and yield under drought: A review","volume":"11","author":"Sarto","year":"2017","journal-title":"Aust. J. Crop Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1080\/07352689.2014.875291","article-title":"Drought stress in wheat during flowering and grain-filling periods","volume":"33","author":"Farooq","year":"2014","journal-title":"Crit. Rev. Plant Sci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"El-Hendawy, S., Mohammed, N., and Al-Suhaibani, N. (2024). Enhancing wheat growth, physiology, yield, and water use efficiency under deficit irrigation by integrating foliar application of salicylic acid and nutrients at critical growth stages. Plants, 13.","DOI":"10.3390\/plants13111490"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kulkarni, M., Soolanayakanahally, R., Ogawa, S., Uga, Y., Selvaraj, M.G., and Kagale, S. (2017). Drought response in wheat: Key genes and regulatory mechanisms controlling root system architecture and transpiration efficiency. Front. Chem., 5.","DOI":"10.3389\/fchem.2017.00106"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1023\/A:1004317523264","article-title":"Root growth and water uptake during water deficit and recovering in wheat","volume":"201","author":"Asseng","year":"1998","journal-title":"Plant Soil"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1365-3040.2009.02059.x","article-title":"The distribution and abundance of wheat roots in a dense, structured subsoil\u2013implications for water uptake","volume":"33","author":"White","year":"2010","journal-title":"Plant Cell Environ."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Fang, Y., Chang, J., Shi, T., Luo, W., Ou, Y., Wan, D., and Li, J. (2021). Evolution of RGF\/GLV\/CLEL peptide hormones and their roles in land plant growth and regulation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413372"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Furumizu, C., and Sawa, S. (2021). The RGF\/GLV\/CLEL family of short peptides evolved through lineage-specific losses and diversification and yet conserves its signaling role between vascular plants and bryophytes. Front. Plant Sci., 12.","DOI":"10.3389\/fpls.2021.703012"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"170556","DOI":"10.1016\/j.peptides.2021.170556","article-title":"Root meristem growth factor RGF, a sulfated peptide hormone in plants","volume":"142","author":"Shinohara","year":"2021","journal-title":"Peptides"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hsiao, Y.C., and Yamada, M. (2020). The roles of peptide hormones and their receptors during plant root development. Genes, 12.","DOI":"10.3390\/genes12010022"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Khalil, H.B., Kamel, A.M., Mohamed, A.Y., Hesham, D., Mahmoud, Y., Ibrahim, R., and Elsayed, M.H. (2023). Emerging roles of melatonin in mitigating pathogen stress. Melatonin: Role in Plant Signaling, Growth and Stress Tolerance: Phytomelatonin in Normal and Challenging Environments, Springer.","DOI":"10.1007\/978-3-031-40173-2_12"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.pbi.2011.10.006","article-title":"Growth and development of the root apical meristem","volume":"15","author":"Perilli","year":"2012","journal-title":"Curr. Opin. Plant Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sattar, A., Sher, A., Ijaz, M., Ul-Allah, S., Abbas, T., Hussain, S., and Ibrahim, M.F. (2023). Silicon and strigolactone application alleviates the adversities of cadmium toxicity in maize by modulating morpho-physiological and antioxidants defense mechanisms. Agronomy, 13.","DOI":"10.3390\/agronomy13092352"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1073\/pnas.1119864109","article-title":"CLE-like (CLEL) peptides control the pattern of root growth and lateral root development in Arabidopsis","volume":"109","author":"Meng","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Delay, C., Imin, N., and Djordjevic, M.A. (2013). Regulation of Arabidopsis root development by small signaling peptides. Front. Plant Sci., 4.","DOI":"10.3389\/fpls.2013.00352"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5245","DOI":"10.1093\/jxb\/erv329","article-title":"The GLV6\/RGF8\/CLEL2 peptide regulates early pericycle divisions during lateral root initiation","volume":"66","author":"Fernandez","year":"2015","journal-title":"J. Exp. Bot."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/978-1-4939-8772-6_9","article-title":"Analysis of PLETHORA gradient formation by secreted peptides during root development","volume":"Volume 1863","author":"Shinohara","year":"2018","journal-title":"Methods in Molecular Biology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/cr.2016.63","article-title":"RGF1 INSENSITIVE 1 to 5, a group of LRR receptor-like kinases, are essential for the perception of root meristem growth factor 1 in Arabidopsis thaliana","volume":"26","author":"Ou","year":"2016","journal-title":"Cell Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"112815","DOI":"10.1016\/j.scienta.2023.112815","article-title":"BAG2 and MAPK2 regulate differently on different periods of heat-induced programmed cell death in tomato","volume":"327","author":"He","year":"2024","journal-title":"Sci. Hortic."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1038\/s41467-026-71645-z","article-title":"Root development progression involves RALF peptide-mediated ROS signaling and pectin dynamics in rice","volume":"17","author":"Jia","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, X., Guo, Z., Lv, Y., Cen, X., Ding, X., Wu, H., Li, X., Huang, J., and Xiong, L. (2017). Genetic control of the root system in rice under normal and drought stress conditions by genome-wide association study. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006889"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kaur, V., Yadav, S.K., Yadav, B., Madaan, S., Kheralia, M., and Chinnusamy, V. (2026). Root system architecture and drought adaptation: Emerging tools and genetic insights. Front. Plant Sci., 17.","DOI":"10.3389\/fpls.2026.1753086"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1071\/FP06055","article-title":"The role of root architectural traits in adaptation of wheat to water-limited environments","volume":"33","author":"Manschadi","year":"2006","journal-title":"Funct. Plant Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1093\/jxb\/ert043","article-title":"Soil conditions and cereal root system architecture: Review and considerations for linking Darwin and Weaver","volume":"64","author":"Rich","year":"2013","journal-title":"J. Exp. Bot."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Tian, D., Xie, Q., Deng, Z., Xue, J., Li, W., Zhang, Z., Dai, Y., Zheng, B., Lu, T., and De Smet, I. (2022). Small secreted peptides encoded on the wheat (Triticum aestivum L.) genome and their potential roles in stress responses. Front. Plant Sci., 13, Correction in Front. Plant Sci.\u00a02022, 13.","DOI":"10.3389\/fpls.2022.1000297"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"35","DOI":"10.5943\/cream\/15\/1\/4","article-title":"Comparative genomic analysis of effector repertoires in rust fungi: Insights into pathogenesis and host interactions in wheat","volume":"15","author":"Khalil","year":"2025","journal-title":"Curr. Res. Environ. Appl. Mycol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.3390\/molecules20022138","article-title":"Tyrosine sulfation as a protein post-translational modification","volume":"20","author":"Yang","year":"2015","journal-title":"Molecules"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Alrajhi, A., Alharbi, S., Beecham, S., and Alotaibi, F. (2024). Regulation of root growth and elongation in wheat. Front. Plant Sci., 15.","DOI":"10.3389\/fpls.2024.1397337"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"El Nabawy, M.H., Najeeb, K.M., Khalil, H.B., Soliman, K.A., and El-Seoudy, A.A. (2025). Integrated phenotypic and molecular evaluation of powdery mildew resistance in Egyptian barley: Identification of resistance-associated markers. Plants, 14.","DOI":"10.3390\/plants14081231"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s43088-025-00697-9","article-title":"Guanine and \u03b2-aminobutyric acid as novel elicitors enhance barley defence against net blotch disease through oxidative stress and enzymatic defence mechanisms","volume":"14","author":"Thabet","year":"2025","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1111\/j.1365-313X.2009.03926.x","article-title":"Regulation and processing of a plant peptide hormone, AtRALF23, in Arabidopsis","volume":"59","author":"Srivastava","year":"2009","journal-title":"Plant J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1126\/science.1191132","article-title":"Secreted peptide signals required for maintenance of root stem cell niche in Arabidopsis","volume":"329","author":"Matsuzaki","year":"2010","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1126\/science.aai8550","article-title":"Precursor processing for plant peptide hormone maturation by subtilisin-like serine proteinases","volume":"354","author":"Schardon","year":"2016","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Khalil, H.B. (2024). Genome-wide characterization and expression profiling of phytosulfokine receptor genes (PSKRs) in Triticum aestivum with docking simulations of their interactions with phytosulfokine (PSK): A bioinformatics study. Genes, 15.","DOI":"10.3390\/genes15101306"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1146\/annurev-arplant-050312-120122","article-title":"Posttranslationally modified small-peptide signals in plants","volume":"65","author":"Matsubayashi","year":"2014","journal-title":"Annu. Rev. Plant Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11205","DOI":"10.1073\/pnas.1308974110","article-title":"Quantitative phosphoproteomics identifies SnRK2 protein kinase substrates and reveals the effectors of abscisic acid action","volume":"110","author":"Wang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1105\/tpc.16.00656","article-title":"The PLETHORA gene regulatory network guides growth and cell differentiation in Arabidopsis roots","volume":"28","author":"Santuari","year":"2016","journal-title":"Plant Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1093\/jxb\/erh276","article-title":"Root growth maintenance during water deficits: Physiology to functional genomics","volume":"55","author":"Sharp","year":"2004","journal-title":"J. Exp. Bot."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/j.1469-8137.2008.02436.x","article-title":"Mechanisms of plant survival and mortality during drought: Why do some plants survive while others succumb to drought?","volume":"178","author":"McDowell","year":"2008","journal-title":"New Phytol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e13651","DOI":"10.1111\/ppl.13651","article-title":"Shaping the root system architecture in plants for adaptation to drought stress","volume":"174","author":"Ranjan","year":"2022","journal-title":"Physiol. Plant."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wang, G., Zhang, G., and Wu, M. (2016). CLE peptide signaling and crosstalk with phytohormones and environmental stimuli. Front. Plant Sci., 6.","DOI":"10.3389\/fpls.2015.01211"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/cr.2016.62","article-title":"Signature motif-guided identification of receptors for peptide hormones essential for root meristem growth","volume":"26","author":"Song","year":"2016","journal-title":"Cell Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1105\/tpc.19.00335","article-title":"Brassinosteroids: Multidimensional regulators of plant growth, development, and stress responses","volume":"32","author":"Nolan","year":"2020","journal-title":"Plant Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1007\/s11427-020-1719-y","article-title":"Understanding the molecular mechanisms of trade-offs between plant growth and immunity","volume":"64","author":"Wang","year":"2021","journal-title":"Sci. China Life Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1016\/j.molp.2020.09.005","article-title":"RGF1-RGI1, a peptide-receptor complex, regulates Arabidopsis root meristem development via a MAPK signaling cascade","volume":"13","author":"Lu","year":"2020","journal-title":"Mol. Plant"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1021\/ja026939x","article-title":"HADDOCK: A protein\u2013protein docking approach based on biochemical or biophysical information","volume":"125","author":"Dominguez","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Kamel, A.M., Metwally, K., Sabry, M., Albalawi, D.A., Abbas, Z.K., Darwish, D.B., and Khalil, H.B. (2023). The expression of Triticum aestivum cysteine-rich receptor-like protein kinase genes during leaf rust fungal infection. Plants, 12.","DOI":"10.3390\/plants12162932"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Khalil, H.B., Zakherah, H.A., Alhassan, F.A., Salah, M.M., Kamel, A.M., Mohamed, A.Y., Alsahoud, H.A., Metwaly, F.H., and Mostafa, S.A. (2026). Wheat plasma membrane receptors: Orchestrating immunity and bridging to crop improvement. Curr. Issues Mol. Biol., 48.","DOI":"10.3390\/cimb48010002"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Khalil, H.B., Lutfi, A.M., Sayed, A.R., Mahmoud, M.T., Mostafa, S.A., Ibrahim, Z.A., and Thabet, M. (2024). Gamma-aminobutyric acid (GABA) as a defense booster for wheat against leaf rust pathogen (Puccinia triticina). Plants, 13.","DOI":"10.3390\/plants13192792"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"20160013","DOI":"10.1098\/rstb.2016.0020","article-title":"The evolution of methods for establishing evolutionary timescales","volume":"371","author":"Donoghue","year":"2016","journal-title":"Philos. Trans. R. Soc. B"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.exer.2014.07.007","article-title":"Role of tyrosine-sulfated proteins in retinal structure and function","volume":"133","author":"Kanan","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1038\/s41467-025-57291-x","article-title":"The TaCLE24b peptide signaling cascade modulates lateral root development and drought tolerance in wheat","volume":"16","author":"Yang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1146\/annurev-arplant-042916-040957","article-title":"The structural basis of ligand perception and signal activation by receptor kinases","volume":"68","author":"Hohmann","year":"2017","journal-title":"Annu. Rev. Plant Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Gasteiger, E., Hoogland, C., Gattiker, A., Duvaud, S.E., Wilkins, M.R., Appel, R.D., and Bairoch, A. (2005). Protein identification and analysis tools on the ExPASy server. The Proteomics Protocols Handbook, Humana Press.","DOI":"10.1385\/1-59259-890-0:571"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"W215","DOI":"10.1093\/nar\/gkae237","article-title":"DeepLoc 2.1: Multi-label membrane protein type prediction using protein language models","volume":"52","author":"Teufel","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"W202","DOI":"10.1093\/nar\/gkp335","article-title":"MEME SUITE: Tools for motif discovery and searching","volume":"37","author":"Bailey","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"W362","DOI":"10.1093\/nar\/gkl124","article-title":"ScanProsite: Detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins","volume":"34","author":"Sigrist","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1093\/molbev\/msab120","article-title":"MEGA11: Molecular evolutionary genetics analysis version 11","volume":"38","author":"Tamura","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"ref_66","first-page":"275","article-title":"The rapid generation of mutation data matrices from protein sequences","volume":"8","author":"Jones","year":"1992","journal-title":"Comput. Appl. Biosci."},{"key":"ref_67","unstructured":"Andrews, S. (2010). FastQC: A Quality Control Tool for High Throughput Sequence Data, Babraham Bioinformatics."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nbt.3122","article-title":"StringTie enables improved reconstruction of a transcriptome from RNA-seq reads","volume":"33","author":"Pertea","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_71","first-page":"1","article-title":"R: A language and environment for statistical computing","volume":"8","author":"Wickham","year":"2019","journal-title":"J. Open Source Softw."},{"key":"ref_72","unstructured":"Reese, M.G., and Eeckman, F.H. (1995, January 16\u201320). Novel neural network algorithms for improved eukaryotic promoter site recognition. Proceedings of the Seventh International Genome Sequencing and Analysis Conference, Hilton Head Island, SC, USA."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1093\/bioinformatics\/15.5.356","article-title":"Promoter2.0: For the recognition of PolII promoter sequences","volume":"15","author":"Knudsen","year":"1999","journal-title":"Bioinformatics"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1093\/nar\/27.1.297","article-title":"Plant cis-acting regulatory DNA elements (PLACE) database: 1999","volume":"27","author":"Higo","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"ref_75","first-page":"D1104","article-title":"PlantRegMap: Charting functional regulatory maps in plants","volume":"48","author":"Tian","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"W288","DOI":"10.1093\/nar\/gks419","article-title":"PEP-FOLD: An updated de novo structure prediction server for both linear and disulfide bonded cyclic peptides","volume":"40","author":"Shen","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"168554","DOI":"10.1016\/j.jmb.2024.168554","article-title":"CHARMM-GUI PDB reader and manipulator: Covalent ligand modeling and simulation","volume":"436","author":"Kong","year":"2024","journal-title":"J. Mol. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","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":"ref_79","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6665","DOI":"10.1073\/pnas.0408037102","article-title":"Potential energy functions for atomic-level simulations of water and organic and biomolecular systems","volume":"102","author":"Jorgensen","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1002\/jcc.23354","article-title":"CHARMM36 all-atom additive protein force field: Validation based on comparison to NMR data","volume":"34","author":"Huang","year":"2013","journal-title":"J. Comput. Chem."},{"key":"ref_82","unstructured":"Case, D.A., Aktulga, H.M., Belfon, K., Ben-Shalom, I.Y., Berryman, J.T., Brozell, S.R., and Kollman, P.A. (2023). Amber 2023, University of California."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1002\/jcc.21209","article-title":"Accelerating molecular dynamic simulation on graphics processing units","volume":"30","author":"Friedrichs","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Eastman, P., Swails, J., Chodera, J.D., McGibbon, R.T., Zhao, Y., Beauchamp, K.A., and Pande, V.S. (2017). OpenMM 7: Rapid development of high-performance algorithms for molecular dynamics. PLoS Comput. Biol., 13.","DOI":"10.1371\/journal.pcbi.1005659"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: A 2D graphics environment","volume":"9","author":"Hunter","year":"2007","journal-title":"Comput. Sci. Eng."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7616\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:03:14Z","timestamp":1787670194000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7616"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":86,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177616"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177616","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]}}}