{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T06:07:59Z","timestamp":1776406079161,"version":"3.51.2"},"reference-count":77,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3n Iberoamericana de Estudios Superiores"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cystic echinococcosis (CE) is an endemic zoonotic disease caused by Echinococcus granulosus, which forms cysts in ungulates\u2019 intermediate hosts. Humans are accidental hosts, and CE affects more than one million people worldwide. Imaging remains the diagnostic gold standard, outperforming serological methods. This study presents an in silico analysis of two glyceraldehyde-3-phosphate dehydrogenase (GAPDH) isoenzymes from E. granulosus (EgGAPDH), isolated from a parasite cell line (EGPE). EgGAPDHs were recognized by sera from CE patients, identified through LC-MS\/MS and PCR of metacestodes from cattle liver. One isoenzyme is intracellular (IC) (UniProt: W6UJ19), and the other is extracellular (EC) (UniProt: W6V1T8). GAPDH is involved in host\u2013parasite interactions and metabolic processes. We characterized the physicochemical properties; linear epitopes (LEPs); and amino acid domains of EgGAPDH, its hosts, and other parasites. W6UJ19 emerged as the most promising isoenzyme as a marker of infection. Molecular dynamics simulations of isoenzymes, performed in the presence or absence of two bisphosphonates (BPs), revealed how drug binding alters conformational epitopes (CEPs) and suggested that W6UJ19 is more responsive to BP modulation. Binding affinity analysis using the MMPBSA method revealed that etidronate (EHDP) binds EgGAPDH with greater affinity than phosphate (Pi) and alendronate (AL), in the following order: EHDP &gt; Pi &gt; AL.<\/jats:p>","DOI":"10.3390\/ijms262110622","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:15:14Z","timestamp":1762175714000},"page":"10622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["First In Silico Study of Two Echinococcus granulosus Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Recognized by Liver Cystic Echinococcosis Human Sera"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2079-7243","authenticated-orcid":false,"given":"Facundo Ariel","family":"Ag\u00fcero","sequence":"first","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Buenos Aires C1270AAH, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires C1270AAH, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Maglioco","sequence":"additional","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Buenos Aires C1270AAH, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires C1270AAH, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3164-4426","authenticated-orcid":false,"given":"Mar\u00eda P\u00eda","family":"Valacco","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires C1270AAH, Argentina"},{"name":"Centro de Estudios Qu\u00edmicos y Biol\u00f3gicos por Espectrometr\u00eda de Masa, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1121ABG, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8275-1549","authenticated-orcid":false,"given":"Alejandra Yaqueline","family":"Ju\u00e1rez Valdez","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires C1270AAH, Argentina"},{"name":"Instituto Nacional de Parasitolog\u00eda \u201cDr. Mario Fatala-Chaben\u201d, Administraci\u00f3n Nacional de Salud \u201cDr. Carlos Malbr\u00e1n\u201d, Buenos Aires C1121ABG, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilio","family":"Rold\u00e1n","sequence":"additional","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Buenos Aires C1270AAH, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margot","family":"Paulino","sequence":"additional","affiliation":[{"name":"Facultad de Qu\u00edmica, Departamento de Experimentaci\u00f3n y Teor\u00eda de la Materia y sus Aplicaciones, \u00c1rea Bioinform\u00e1tica, Universidad de la Rep\u00fablica, Montevideo CP 12900, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicia Graciela","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Buenos Aires C1270AAH, Argentina"},{"name":"Instituto Nacional de Parasitolog\u00eda \u201cDr. Mario Fatala-Chaben\u201d, Administraci\u00f3n Nacional de Salud \u201cDr. Carlos Malbr\u00e1n\u201d, Buenos Aires C1121ABG, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1051\/parasite\/2020024","article-title":"International consensus on terminology to be used in the field of echinococcoses","volume":"27","author":"Vuitton","year":"2020","journal-title":"Parasite"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/tmi.12647","article-title":"Cystic echinococcosis in South America: Systematic review of species and genotypes of Echinococcus granulosus sensu lato in humans and natural domestic hosts","volume":"21","author":"Cucher","year":"2016","journal-title":"Trop. Med. Int. Health"},{"key":"ref_3","unstructured":"(2023, April 19). Equinococosis. Available online: https:\/\/www.who.int\/es\/news-room\/fact-sheets\/detail\/echinococcosis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s00436-021-07048-4","article-title":"First report of Cystic echinococcosis caused by Echinococcus granulosus sensu stricto\/G1 in Felix catus from the Patagonian region of Argentina","volume":"120","author":"Avila","year":"2021","journal-title":"Parasitol. Res."},{"key":"ref_5","first-page":"88","article-title":"Hidatidosis una zoonosis de distribuci\u00f3n mundial","volume":"27","year":"2008","journal-title":"ofFARM"},{"key":"ref_6","first-page":"41","article-title":"Hydatidosis: Clinical-imaging classification according to Gharbi and the World Health Organization","volume":"86","author":"Calaramo","year":"2022","journal-title":"Rev. Argent. Radiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Tamarozzi, F., Silva, R., Fittipaldo, V.A., Buonfrate, D., Gottstein, B., and Siles Lucas, M. (2021). Serology for the diagnosis of human hepatic cystic echinococcosis and its relation with cyst staging: A systematic review of the literature with meta-analysis. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009370"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e0064","DOI":"10.1128\/IAI.00641-19","article-title":"Particles from the Echinococcus granulosus laminated layer Inhibit CD40 upregulation in dendritic cells by interfering with Akt activation","volume":"87","author":"Pittini","year":"2019","journal-title":"Infect. Immun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1046\/j.1365-3024.1998.00117.x","article-title":"Diagnostic evaluation of a synthetic peptide derived from a novel antigen B subunit as related to other available peptides and native antigens used for serology of cystic hydatidosis","volume":"20","author":"Barbieri","year":"1998","journal-title":"Parasite Immunol."},{"key":"ref_10","first-page":"358","article-title":"Evaluation of the ability of antigen B originated from Echinococcus granulosus sensu stricto and E. Canadensis for the diagnosis of confirmed human cystic echinococcosis using ELISA","volume":"17","author":"Sadjjadi","year":"2022","journal-title":"Iran J. Parasitol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s11626-010-9345-8","article-title":"Morphological and biological characterization of cell line developed from bovine Echinococcus granulosus","volume":"46","author":"Isolabella","year":"2010","journal-title":"Vitr. Cell. Dev. Biol. Anim."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e12674","DOI":"10.1111\/pim.12674","article-title":"Detection of Echinococcus granulosus sensu lato infection by using extracts derived from a protoscoleces G1 cell line","volume":"41","author":"Maglioco","year":"2019","journal-title":"Parasite Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Maglioco, M., Ag\u00fcero, F.A., Valacco, M.P., Ju\u00e0rez Valdez, A., Paulino, M., and Fuchs, A.G. (2022). Characterization of the B-Cell Epitopes of Echinococcus granulosus histones H4 and H2A recognized by sera from patients with liver cysts. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.901994"},{"key":"ref_14","first-page":"1672","article-title":"Sperm-specific glyceraldehyde-3-phosphate dehydrogenase\u2014An evolutionary acquisition of mammals","volume":"80","author":"Muronetz","year":"2015","journal-title":"Biochemistry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1186\/s13071-017-2359-2","article-title":"Fasciclin-calcareous corpuscle binary complex mediated protein-protein interactions in Taenia solium metacestode","volume":"10","author":"Ahn","year":"2017","journal-title":"Parasit. Vectors."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6666","DOI":"10.1038\/s41467-021-27056-3","article-title":"GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain","volume":"12","author":"Dar","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"105036","DOI":"10.1016\/j.actatropica.2019.05.027","article-title":"Identification and molecular characterization of exosome-like vesicles derived from the Taenia asiatica adult worm","volume":"198","author":"Liang","year":"2019","journal-title":"Acta Trop."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/0014-5793(95)00023-3","article-title":"The effect of iron status on glyceraldehyde 3-phosphate dehydrogenase expression in rat liver","volume":"359","author":"Quail","year":"1995","journal-title":"FEBS Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1046\/j.1365-2958.2003.03518.x","article-title":"Surface localized glyceraldehyde-3-phosphate dehydrogenase of Mycoplasma genitalium binds mucin","volume":"48","author":"Alvarez","year":"2003","journal-title":"Mol. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3900","DOI":"10.1128\/IAI.00611-12","article-title":"Comparative transcriptomic and proteomic analyze of Trichomonas vaginalis following adherence to fibronectin","volume":"8","author":"Huang","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.freeradbiomed.2021.07.037","article-title":"Oxidized GAPDH transfers S-glutathionylation to a nuclear protein Sirtuin-1 leading to apoptosis","volume":"174","author":"Rizvi","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1128\/IAI.00157-09","article-title":"Glyceraldehyde-3-phosphate dehydrogenase is a surface-associated, fibronectin-binding protein of Trichomonas vaginalis","volume":"77","author":"Lama","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1517\/13543776.2011.593511","article-title":"Farnesyl pyrophosphate synthase modulators: A patent review (2006\u20132010)","volume":"21","author":"Sun","year":"2011","journal-title":"Expert. Opin. Ther. Pat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ceca.2011.05.012","article-title":"Acidocalcisomes","volume":"50","author":"Docampo","year":"2011","journal-title":"Cell Calcium."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrmicro1097","article-title":"Acidocalcisomes\u2014Conserved from bacteria to man","volume":"3","author":"Docampo","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00535-20","DOI":"10.1128\/AAC.00535-20","article-title":"Orally bioavailable endochin-like quinolone carbonate ester prodrug reduces Toxoplasma gondii brain cysts","volume":"64","author":"Doggett","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1128\/EC.00271-13","article-title":"Solanesyl diphosphate synthase, an enzyme of the ubiquinone synthetic pathway, is required throughout the life cycle of Trypanosoma brucei","volume":"13","author":"Lai","year":"2014","journal-title":"Eukaryot. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sleda, M.A., Li, Z.H., Behera, R., Baierna, B., Li, C., Jumpathong, J., Malwal, S.R., Kawamukai, M., Oldfield, E., and Moreno, S.N.J. (2022). The heptaprenyl diphosphate synthase (Coq1) is the target of a lipophilic bisphosphonate that protects mice against Toxoplasma gondii Infection. mBio, 13.","DOI":"10.1128\/mbio.01966-22"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sleda, M.A., Pitafi, Z.F., Song, W., Oldfield, E., and Moreno, S.N.J. (2024). Lipophilic bisphosphonates reduced cyst burden and ameliorated hyperactivity of mice chronically infected with Toxoplasma gondii. mBio, 15.","DOI":"10.1128\/mbio.01756-24"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Valenti, M.T., Bertoldo, F., Dalle Carbonare, L., Azzarello, G., Zenari, S., Zanatta, M., Balducci, E., Vinante, O., and Lo Cascio, V. (2006). The effect of bisphosphonates on gene expression: GAPDH as a housekeeping or a new target gene?. BMC Cancer, 6.","DOI":"10.1186\/1471-2407-6-49"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1017\/S0022149X13000436","article-title":"Proline modulates the effect of bisphosphonate on calcium levels and adenosine triphosphate production in cell lines derived from bovine Echinococcus granulosus protoscoleces","volume":"88","author":"Fuchs","year":"2014","journal-title":"J. Helminthol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2174\/1874421401907010019","article-title":"Effect of etidronate and ibandronate on cytosolic Ca2+ in HT29 and parasite cell line from Echinococcus granulosus sensu lato","volume":"7","author":"Ferrulli","year":"2019","journal-title":"Open Parasitol. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.bone.2011.03.774","article-title":"The relationship between the chemistry and biological activity of the bisphosphonates","volume":"49","author":"Ebetino","year":"2011","journal-title":"Bone"},{"key":"ref_34","first-page":"75","article-title":"Effect of mebendazole and praziquantel on glucosephosphate isomerase and glyceraldehydephosphate dehydrogenase in Echinococcus granulosus cyst wall harbored in mice","volume":"18","author":"You","year":"1997","journal-title":"Zhongguo Yao Li Xue Bao"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1016\/S0020-7519(01)00244-2","article-title":"Immunisation with Salmonella typhimurium-delivered glyceraldehyde-3-phosphate dehydrogenase protects mice against challenge infection with Echinococcus multilocularis eggs","volume":"31","author":"Beyer","year":"2001","journal-title":"Int. J. Parasitol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1046\/j.1365-2184.2002.00236.x","article-title":"Proliferative and nutritional dependent regulation of glyceraldehyde-3-phosphate dehydrogenase expression in the rat liver","volume":"35","author":"Corbin","year":"2002","journal-title":"Cell Prolif."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S0022-2836(75)80055-6","article-title":"Analysis of the allosteric basis for positive and negative co-operativity and half-of-the-sites reactivity in yeast and rabbit muscle glyceraldehyde 3-phosphate dehydrogenase","volume":"87","author":"Herzfeld","year":"1975","journal-title":"J. Mol. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1083\/jcb.130.5.1093","article-title":"A mutation in glyceraldehyde 3-phosphate dehydrogenase alters endocytosis in CHO cells","volume":"130","author":"Robbins","year":"1995","journal-title":"J. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Iwai, K., Shibukawa, Y., Yamazaki, N., and Wada, Y. (2014). Transglutaminase 2-dependent deamidation of glyceraldehyde-3-phosphate dehydrogenase promotes trophoblastic cell fusion. J. Biol. Chem., 289.","DOI":"10.1074\/jbc.M113.525568"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"20395","DOI":"10.1074\/jbc.M210824200","article-title":"Participation of a fusogenic protein, glyceraldehyde-3-phosphate dehydrogenase, in nuclear membrane assembly","volume":"278","author":"Nakagawa","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"114577","DOI":"10.1016\/j.expneurol.2023.114577","article-title":"Role of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in autophagy activation following subarachnoid hemorrhage","volume":"371","author":"Huo","year":"2024","journal-title":"Exp. Neurol."},{"key":"ref_42","first-page":"593","article-title":"Acceleration of glycolysis in the presence of the non-phosphorylating and the oxidized phosphorylating glyceraldehyde-3-phosphate dehydrogenases","volume":"68","author":"Schmalhausen","year":"2003","journal-title":"Biochemistry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6152","DOI":"10.1074\/jbc.M310549200","article-title":"Rapid shortening of telomere length in response to ceramide involves the inhibition of telomere binding activity of nuclear glyceraldehyde-3-phosphate dehydrogenase","volume":"279","author":"Sundararajj","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1074\/jbc.M114.618165","article-title":"A dimer interface mutation in glyceraldehyde-3-phosphate dehydrogenase regulates its binding to AU-rich RNA","volume":"290","author":"White","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Das, P., Mukherjee, A., and Adak, S. (2021). Glyceraldehyde-3-phosphate dehydrogenase present in extracellular vesicles from Leishmania major suppresses host TNF-alpha expression. J. Biol. Chem., 297.","DOI":"10.1016\/j.jbc.2021.101198"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Maglioco, A., Miana, V., Valacco, M.P., Ag\u00fcero, F.A., Gertiser, M.L., Avila, H.G., Barbery Venturi, M.S., Jensen, O., Ju\u00e1rez Valdez, A.Y., and Prieto Gonz\u00e1lez, E.A. (2025). First comparative proteomic and in vitro behavioral study of Echinococcus granulosus metacestodes in Felis catus. Front. Veter-Sci., 12.","DOI":"10.3389\/fvets.2025.1546420"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13567-021-00952-8","article-title":"Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) moonlights as an adhesin in Mycoplasma hyorhinis adhesion to epithelial cells as well as a plasminogen receptor mediating extracellular matrix degradation","volume":"52","author":"Wang","year":"2021","journal-title":"Vet. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1128\/IAI.74.1.382-389.2006","article-title":"Glyceraldehyde-3-phosphate dehydrogenase of Paracoccidioides brasiliensis is a cell surface protein involved in fungal adhesion to extracellular matrix proteins and interaction with cells","volume":"74","author":"Barbosa","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"S150","DOI":"10.1542\/peds.2006-2023H","article-title":"Bisphosphonates: Mode of action and pharmacology","volume":"2","author":"Russell","year":"2007","journal-title":"Pediatrics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1104\/pp.90.4.1275","article-title":"Phosphate starvation inducible; bypasses\u2019 of adenylate and phosphate dependent glycolytic enzymes in Brassica nigra suspension cells","volume":"90","author":"Duff","year":"1989","journal-title":"Plant Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1042\/bj2750767","article-title":"Alkylation of glyceraldehyde-3-phosphate dehydrogenase with haloacetylphosphonates. An unusual pH-dependence","volume":"275","author":"Li","year":"1991","journal-title":"Biochem. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/BF02408621","article-title":"Effect of diphosphonates on glycogen content of rabbit ear cartilage cells in culture","volume":"30","author":"Felix","year":"1980","journal-title":"Calcif. Tissue Int."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1007\/BF01964068","article-title":"Effect of diphosphonates on ATP and Pi content, Pi uptake and energy charge of cultured calvaria cells","volume":"8","author":"Felix","year":"1982","journal-title":"Experientia"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Cancela, M., Paes, J.A., Moura, H., Barr, J.R., Zaha, A., and Ferreira, H.B. (2019). Unraveling oxidative stress response in the cestode parasite Echinococcus granulosus. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-52456-3"},{"key":"ref_55","unstructured":"Fleisch, H. (2000). Bisphosphonates in Bone Disease: From the Laboratory to the Patients, Academic Press. [4th ed.]."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s00198-007-0540-8","article-title":"Mechanisms of action of bisphosphonates: Similarities and differences and their potential influence on clinical efficacy","volume":"19","author":"Russell","year":"2007","journal-title":"Osteoporos. Int."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ye, P., Yang, Y., Qu, Y., Yang, W., Tan, J., Zhang, C., Sun, D., Zhang, J., Zhao, W., and Guo, S. (2024). LL-37 and bisphosphonate co-delivery 3D-scaffold with antimicrobial and antiresorptive activities for bone regeneration. Int. J. Biol. Macromol., 277.","DOI":"10.1016\/j.ijbiomac.2024.134091"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.cell.2018.08.070","article-title":"The mevalonate pathway is a druggable target for vaccine adjuvant discovery","volume":"175","author":"Xia","year":"2018","journal-title":"Cell"},{"key":"ref_59","unstructured":"(2023, June 28). Available online: https:\/\/www.uniprot.org\/uniprotkb?query=%22Glyceraldehyde%203-phosphate%20dehydrogenase%22%20AND%20(taxonomy_id:6210)."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ye, J., Coulouris, G., Zaretskaya, I., Cutcutache, I., Rozen, S., and Madden, T.L. (2012). Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction. BMC Bioinform., 3.","DOI":"10.1186\/1471-2105-13-134"},{"key":"ref_61","first-page":"531","article-title":"Protein identification and analysis tools in the ExPASy server","volume":"12","author":"Wilkins","year":"1999","journal-title":"Methods Mol. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0968-0004(99)01540-6","article-title":"NPS@: Network protein sequence analysis","volume":"25","author":"Combet","year":"2000","journal-title":"Trends Biochem. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"D412","DOI":"10.1093\/nar\/gkaa913","article-title":"Pfam: The protein families database in 2021","volume":"49","author":"Mistry","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"D265","DOI":"10.1093\/nar\/gkz991","article-title":"CDD\/SPARCLE: The conserved domain database in 2020","volume":"48","author":"Lu","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"D418","DOI":"10.1093\/nar\/gkac993","article-title":"InterPro in 2022","volume":"51","author":"Blum","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nprot.2015.053","article-title":"The Phyre2 web portal for protein modeling, prediction and analysis","volume":"10","author":"Kelley","year":"2015","journal-title":"Nat. Protoc."},{"key":"ref_67","first-page":"3886","article-title":"af3cli: Streamlining AlphaFold3 Input Preparation","volume":"5","author":"Kemnitz","year":"2025","journal-title":"J. Chem. Inf. Model."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"W407","DOI":"10.1093\/nar\/gkm290","article-title":"ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins","volume":"35","author":"Wiederstein","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/prot.22234","article-title":"Protonate3D: Assignment of ionization states and hydrogen coordinates to macromolecular structures","volume":"75","author":"Labute","year":"2009","journal-title":"Proteins"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"044130","DOI":"10.1063\/5.0014475","article-title":"Scalable molecular dynamics on CPU and GPU architectures with NAMD","volume":"153","author":"Phillips","year":"2020","journal-title":"J. Chem. Phys."},{"key":"ref_71","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_72","unstructured":"(2025, October 26). Molecular Operating Environment. Available online: https:\/\/www.chemcomp.com\/en\/Products.htm."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Ribeiro, J.V., Bernardi, R.C., Rudack, T., Stone, J.E., Phillips, J.C., Freddolino, P.L., and Schulten, K. (2016). QwikMD\u2009-\u2009Integrative Molecular Dynamics Toolkit for Novices and Experts. Sci. Rep., 6.","DOI":"10.1038\/srep26536"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/prot.21078","article-title":"Prediction of continuous B-cell epitopes in an antigen using recurrent neural network","volume":"65","author":"Saha","year":"2006","journal-title":"Proteins"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"D436","DOI":"10.1093\/nar\/gkae1092","article-title":"The Immune Epitope Database (IEDB): 2024 update","volume":"53","author":"Vitam","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"W140","DOI":"10.1093\/nar\/gkaa275","article-title":"MusiteDeep: A deep-learning based webserver for protein post-translational modification site prediction and visualization","volume":"48","author":"Wang","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.gpb.2018.04.007","article-title":"DeepNitro: Prediction of Protein Nitration and Nitrosylation Sites by Deep Learning","volume":"16","author":"Xie","year":"2018","journal-title":"Genom. Proteom. Bioinf."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10622\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:20:49Z","timestamp":1762176049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":77,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262110622"],"URL":"https:\/\/doi.org\/10.3390\/ijms262110622","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,31]]}}}