{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T06:37:06Z","timestamp":1772087826625,"version":"3.50.1"},"reference-count":108,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Echinococcosis is a significant parasitic zoonotic disease with severe implications for human and animal health. To date, there has been no effective vaccine candidate available for echinococcosis. Therefore, we employed computational approaches to develop a multiepitope-based vaccine using the most potent epitopes of MHC-I, MHC-II, and B-cell derived from the Ag5 protein of <jats:italic>Echinococcus<\/jats:italic> spp. The final vaccine construct containing the epitopes, linkers, and adjuvant exhibited potent antigenicity (score &gt; 0.1) with no evidence of allergenicity (score &lt; 0) and toxicity (score &lt; 0) in several computational platforms. The vaccine also exhibited favorable physicochemical characteristics such as being highly soluble (SOLpro score of 0.781243) and hydrophilic (Grand average of hydropathy of -0.433). Moreover, the tertiary structure of the vaccine was also found to be structurally stable, with a Z score of -5.71. Further, the molecular docking analysis confirmed the vaccine\u2019s significant binding affinity to the RP-105 (docking score of -1252.7) and TLR-9 (docking score of -970.9). The molecular dynamic simulations confirmed the structural stability of the docked complexes under a virtual physiological system. The negative \u0394TOTAL values derived from the MM-PBSA and MM-GBSA analyses confirmed a spontaneous and thermodynamically favorable binding process between the vaccine and receptors. Moreover, the vaccine demonstrated high potentiality to elicit both innate (natural killer cell, dendritic and macrophage) and adaptive (B-cell, helper T cell and cytotoxic T cell) immune responses with sustained humoral immune responses evidenced by increased IFN-\u03b3 and IL-2 levels. Following codon optimization and <jats:italic>in silico<\/jats:italic> cloning, the vaccine was successfully expressed (CAI value of 0.9607 and average GC content of 52.34%) after being inserted into the pET-28a (+) plasmid of <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic>. These findings highlight the potential of the designed vaccine candidate to combat echinococcosis and lay the groundwork for future preclinical and clinical studies.<\/jats:p>","DOI":"10.1371\/journal.pone.0310510","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T18:26:51Z","timestamp":1739384811000},"page":"e0310510","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Designing of a multiepitope-based vaccine against echinococcosis utilizing the potent Ag5 antigen: Immunoinformatics and simulation approaches"],"prefix":"10.1371","volume":"20","author":[{"given":"Rehana","family":"Parvin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Md. Habib Ullah","family":"Masum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Homaira Pervin","family":"Heema","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aklima","family":"Akter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Alamgir","family":"Hossain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2990-4022","authenticated-orcid":true,"given":"A. M. A. M. Zonaed","family":"Siddiki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"pone.0310510.ref001","doi-asserted-by":"crossref","first-page":"80","DOI":"10.20546\/ijcmas.2016.508.010","article-title":"Prevalence of Parasitic Helminthes among Slaughtered Animals in Slaughterhouses in Taiz, Yemen","volume":"5","author":"K Hezam","year":"2016","journal-title":"International Journal of Current Microbiology and Applied Sciences"},{"issue":"2","key":"pone.0310510.ref002","first-page":"125","article-title":"Echinococcosis: a review","volume":"13","author":"P Moro","year":"2009","journal-title":"International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases"},{"issue":"3","key":"pone.0310510.ref003","doi-asserted-by":"crossref","first-page":"415","DOI":"10.2460\/ajvr.1980.41.03.415","article-title":"Echinococcus granulosus in dogs in Bangladesh","volume":"41","author":"AW Islam","year":"1980","journal-title":"American journal of veterinary research"},{"issue":"2","key":"pone.0310510.ref004","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1080\/00034983.1977.11687185","article-title":"Hydatid cysts in bovines, caprines and ovines in Dacca, Bangladesh","volume":"71","author":"N Islam","year":"1977","journal-title":"Annals of tropical medicine and parasitology"},{"issue":"4","key":"pone.0310510.ref005","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1002\/vms3.465","article-title":"Major zoonotic diseases of public health importance in Bangladesh","volume":"7","author":"S Chowdhury","year":"2021","journal-title":"Veterinary medicine and science"},{"issue":"1","key":"pone.0310510.ref006","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3855\/jidc.4934","article-title":"Abdominal cystic echinococcosis in Bangladesh: a hospital-based study","volume":"9","author":"MF Karim","year":"2015","journal-title":"Journal of infection in developing countries"},{"key":"pone.0310510.ref007","first-page":"289","article-title":"Molecular Characterization of Echinococcus granulosus through Amplification of 12S rRNA Gene and Cox1 Gene Fragments from Cattle in Chittagong, Bangladesh","volume":"11","author":"M Faruk","year":"2017","journal-title":"International Journal of Biological, Biomolecular, Agricultural, Food and Biotechnological Engineering"},{"issue":"3","key":"pone.0310510.ref008","doi-asserted-by":"crossref","first-page":"391","DOI":"10.5713\/ajas.2013.13386","article-title":"Impact of echinococcosis on quality of sheep meat in the South eastern Kazakhstan","volume":"27","author":"Z Valieva","year":"2014","journal-title":"Asian-Australasian journal of animal sciences"},{"issue":"8","key":"pone.0310510.ref009","article-title":"Complete mitochondrial genomes confirm the generic placement of the plateau vole, Neodon fuscus","volume":"39","author":"JQ Li","year":"2019","journal-title":"Bioscience reports"},{"key":"pone.0310510.ref010","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":"DA Vuitton","year":"2020","journal-title":"Parasite (Paris, France)"},{"issue":"2","key":"pone.0310510.ref011","article-title":"Echinococcosis: Advances in the 21st Century","volume":"32","author":"H Wen","year":"2019","journal-title":"Clinical microbiology reviews"},{"key":"pone.0310510.ref012","doi-asserted-by":"crossref","first-page":"93","DOI":"10.5455\/IJE.2022.09.012","article-title":"Investigation of Echinococcus granulosus in Stray Dogs by Real Time PCR in Izmir Province, Turkey","volume":"1","author":"O Yilmaz","year":"2022","journal-title":"International Journal of Echinococcoses"},{"issue":"6","key":"pone.0310510.ref013","doi-asserted-by":"crossref","first-page":"e2249","DOI":"10.1371\/journal.pntd.0002249","article-title":"A systematic review of the epidemiology of echinococcosis in domestic and wild animals","volume":"7","author":"B Otero-Abad","year":"2013","journal-title":"PLoS neglected tropical diseases"},{"issue":"3","key":"pone.0310510.ref014","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.actatropica.2004.07.001","article-title":"Echinococcus granulosus cattle strain identification in an autochthonous case of cystic echinococcosis in central Mexico","volume":"92","author":"P Maravilla","year":"2004","journal-title":"Acta tropica"},{"key":"pone.0310510.ref015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biologicals.2017.10.003","article-title":"Current status and future prospective of vaccine development against Echinococcus granulosus","volume":"51","author":"MM Pourseif","year":"2018","journal-title":"Biologicals: journal of the International Association of Biological Standardization"},{"key":"pone.0310510.ref016","doi-asserted-by":"crossref","first-page":"668492","DOI":"10.3389\/fimmu.2021.668492","article-title":"Design of a Novel Multi-Epitope Vaccine Against Echinococcus granulosus in Immunoinformatics","volume":"12","author":"M Yu","year":"2021","journal-title":"Frontiers in immunology"},{"issue":"3","key":"pone.0310510.ref017","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.str.2005.02.002","article-title":"Usefulness and limitations of normal mode analysis in modeling dynamics of biomolecular complexes","volume":"13","author":"J Ma","year":"2005","journal-title":"Structure (London, England: 1993)"},{"key":"pone.0310510.ref018","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.meegid.2019.04.017","article-title":"Bioinformatics analysis of EgA31 and EgG1Y162 proteins for designing a multi-epitope vaccine against Echinococcus granulosus","volume":"73","author":"X Zhao","year":"2019","journal-title":"Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases"},{"key":"pone.0310510.ref019","doi-asserted-by":"crossref","first-page":"118633","DOI":"10.1016\/j.molliq.2022.118633","article-title":"Designing AbhiSCoVac\u2014A single potential vaccine for all \u2018corona culprits\u2019: Immunoinformatics and immune simulation approaches","volume":"351","author":"A Choudhury","year":"2022","journal-title":"Journal of Molecular Liquids"},{"key":"pone.0310510.ref020","doi-asserted-by":"crossref","first-page":"105237","DOI":"10.1016\/j.meegid.2022.105237","article-title":"Designing efficient multi-epitope peptide-based vaccine by targeting the antioxidant thioredoxin of bancroftian filarial parasite","volume":"98","author":"S Gorai","year":"2022","journal-title":"Infection, Genetics and Evolution"},{"key":"pone.0310510.ref021","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/978-1-0716-3239-0_29","volume-title":"Computational Vaccine Design","author":"A Chakraborty","year":"2023"},{"key":"pone.0310510.ref022","doi-asserted-by":"crossref","first-page":"109639","DOI":"10.1016\/j.intimp.2022.109639","article-title":"Reverse vaccinology assisted design of a novel multi-epitope vaccine to target Wuchereria bancrofti cystatin: An immunoinformatics approach","volume":"115","author":"NC Das","year":"2023","journal-title":"International Immunopharmacology"},{"key":"pone.0310510.ref023","doi-asserted-by":"crossref","first-page":"104633","DOI":"10.1016\/j.meegid.2020.104633","article-title":"Designing of a novel multi-epitope peptide based vaccine against Brugia malayi: An in silico approach","volume":"87","author":"NC Das","year":"2021","journal-title":"Infection, Genetics and Evolution"},{"issue":"4","key":"pone.0310510.ref024","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s12026-023-09374-4","article-title":"Designing of multi-epitope peptide vaccine against Acinetobacter baumannii through combined immunoinformatics and protein interaction-based approaches","volume":"71","author":"J Dey","year":"2023","journal-title":"Immunologic research"},{"issue":"5","key":"pone.0310510.ref025","doi-asserted-by":"crossref","DOI":"10.3390\/vaccines10050665","article-title":"Designing of a Novel Multi-Antigenic Epitope-Based Vaccine against E. hormaechei: An Intergraded Reverse Vaccinology and Immunoinformatics Approach","volume":"10","author":"TH Albekairi","year":"2022","journal-title":"Vaccines"},{"issue":"2","key":"pone.0310510.ref026","doi-asserted-by":"crossref","DOI":"10.3390\/vaccines11020221","article-title":"Immunoinformatics Approaches for Vaccine Design: A Fast and Secure Strategy for Successful Vaccine Development","volume":"11","author":"SS Rawat","year":"2023","journal-title":"Vaccines"},{"issue":"6","key":"pone.0310510.ref027","article-title":"Multi-Epitope Vaccine Design Using an Immunoinformatic Approach for SARS-CoV-2","volume":"10","author":"Y Feng","year":"2021","journal-title":"Pathogens (Basel, Switzerland)"},{"issue":"1","key":"pone.0310510.ref028","doi-asserted-by":"crossref","first-page":"13836","DOI":"10.1038\/s41598-021-93266-w","article-title":"An immunoinformatics approach to design a multi-epitope vaccine against Mycobacterium tuberculosis exploiting secreted exosome proteins","volume":"11","author":"R Sharma","year":"2021","journal-title":"Scientific Reports"},{"issue":"2","key":"pone.0310510.ref029","doi-asserted-by":"crossref","first-page":"e24186","DOI":"10.1016\/j.heliyon.2024.e24186","article-title":"Multi-epitopes vaccine design for surface glycoprotein against SARS-CoV-2 using immunoinformatic approach","volume":"10","author":"SF Arshad","year":"2024","journal-title":"Heliyon"},{"key":"pone.0310510.ref030","doi-asserted-by":"crossref","first-page":"1091004","DOI":"10.3389\/fimmu.2022.1091004","article-title":"A multi-epitope vaccine GILE against Echinococcus Multilocularis infection in mice","volume":"13","author":"P Zhou","year":"2022","journal-title":"Frontiers in immunology"},{"issue":"4","key":"pone.0310510.ref031","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/s10989-022-10421-1","article-title":"Production and Evaluation of a Novel Multi-Epitope Bivalent Vaccine Against Echinococcus multilocaularis Metacestode","volume":"28","author":"R Li","year":"2022","journal-title":"International Journal of Peptide Research and Therapeutics"},{"key":"pone.0310510.ref032","doi-asserted-by":"crossref","first-page":"100464","DOI":"10.1016\/j.imu.2020.100464","article-title":"Multi-epitope vaccine against cystic echinococcosis using immunodominant epitopes from EgA31 and EgG1Y162 antigens","volume":"21","author":"H Nourmohammadi","year":"2020","journal-title":"Informatics in Medicine Unlocked"},{"issue":"W1","key":"pone.0310510.ref033","doi-asserted-by":"crossref","first-page":"W580","DOI":"10.1093\/nar\/gkv279","article-title":"The EMBL-EBI bioinformatics web and programmatic tools framework","volume":"43","author":"W Li","year":"2015","journal-title":"Nucleic acids research"},{"issue":"14","key":"pone.0310510.ref034","first-page":"1837","article-title":"The design of Jemboss: a graphical user interface to EMBOSS","volume":"19","author":"T Carver","year":"2003","journal-title":"Bioinformatics (Oxford, England)"},{"issue":"Web Server issue","key":"pone.0310510.ref035","doi-asserted-by":"crossref","first-page":"W509","DOI":"10.1093\/nar\/gkn202","article-title":"NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8\u201311","volume":"36","author":"C Lundegaard","year":"2008","journal-title":"Nucleic acids research"},{"issue":"W1","key":"pone.0310510.ref036","doi-asserted-by":"crossref","first-page":"W449","DOI":"10.1093\/nar\/gkaa379","article-title":"NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data","volume":"48","author":"B Reynisson","year":"2020","journal-title":"Nucleic acids research"},{"issue":"9","key":"pone.0310510.ref037","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.4049\/jimmunol.1700893","article-title":"NetMHCpan-4.0: Improved Peptide-MHC Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data","volume":"199","author":"V Jurtz","year":"2017","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"issue":"1","key":"pone.0310510.ref038","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1471-2105-8-4","article-title":"VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines","volume":"8","author":"IA Doytchinova","year":"2007","journal-title":"BMC bioinformatics"},{"issue":"6","key":"pone.0310510.ref039","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1007\/s00894-014-2278-5","article-title":"AllerTOP v.2\u2014a server for in silico prediction of allergens","volume":"20","author":"I Dimitrov","year":"2014","journal-title":"Journal of molecular modeling"},{"issue":"6","key":"pone.0310510.ref040","first-page":"846","article-title":"AllergenFP: allergenicity prediction by descriptor fingerprints","volume":"30","author":"I Dimitrov","year":"2014","journal-title":"Bioinformatics (Oxford, England)"},{"key":"pone.0310510.ref041","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/1471-2105-5-133","article-title":"Allermatch, a webtool for the prediction of potential allergenicity according to current FAO\/WHO Codex alimentarius guidelines","volume":"5","author":"MW Fiers","year":"2004","journal-title":"BMC bioinformatics"},{"issue":"9","key":"pone.0310510.ref042","doi-asserted-by":"crossref","first-page":"e73957","DOI":"10.1371\/journal.pone.0073957","article-title":"In Silico Approach for Predicting Toxicity of Peptides and Proteins","volume":"8","author":"Open Source Drug Discovery C","year":"2013","journal-title":"PLOS ONE"},{"key":"pone.0310510.ref043","doi-asserted-by":"crossref","unstructured":"Rathore A, Arora A, Choudhury S, Tijare P, Raghava G. ToxinPred 3.0: An improved method for predicting the toxicity of peptides2023.","DOI":"10.1101\/2023.08.11.552911"},{"issue":"6","key":"pone.0310510.ref044","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1021\/acs.jproteome.9b00874","article-title":"Improved Prediction of MHC II Antigen Presentation through Integration and Motif Deconvolution of Mass Spectrometry MHC Eluted Ligand Data","volume":"19","author":"B Reynisson","year":"2020","journal-title":"Journal of proteome research"},{"key":"pone.0310510.ref045","doi-asserted-by":"crossref","first-page":"102706","DOI":"10.1016\/j.bcab.2023.102706","article-title":"Construction of a multi-epitope in silico vaccine against Anaplasma Marginale using immunoinformatics approach","volume":"50","author":"AZ Siddiki","year":"2023","journal-title":"Biocatalysis and Agricultural Biotechnology"},{"issue":"W1","key":"pone.0310510.ref046","doi-asserted-by":"crossref","first-page":"W24","DOI":"10.1093\/nar\/gkx346","article-title":"BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes","volume":"45","author":"MC Jespersen","year":"2017","journal-title":"Nucleic acids research"},{"issue":"3","key":"pone.0310510.ref047","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1128\/jvi.55.3.836-839.1985","article-title":"Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide","volume":"55","author":"EA Emini","year":"1985","journal-title":"Journal of virology"},{"issue":"5","key":"pone.0310510.ref048","doi-asserted-by":"crossref","first-page":"e0285177","DOI":"10.1371\/journal.pone.0285177","article-title":"In silico design and validation of a novel multi-epitope vaccine candidate against structural proteins of Chikungunya virus using comprehensive immunoinformatics analyses","volume":"18","author":"S Mahmoodi","year":"2023","journal-title":"PLoS One"},{"key":"pone.0310510.ref049","first-page":"571","volume":"1122007","author":"E Gasteiger","journal-title":"Protein Identification and Analysis Tool on the ExPASy Server"},{"issue":"17","key":"pone.0310510.ref050","first-page":"2200","article-title":"SOLpro: accurate sequence-based prediction of protein solubility","volume":"25","author":"CN Magnan","year":"2009","journal-title":"Bioinformatics (Oxford, England)"},{"issue":"suppl_2","key":"pone.0310510.ref051","doi-asserted-by":"crossref","first-page":"W202","DOI":"10.1093\/nar\/gkl343","article-title":"AlgPred: prediction of allergenic proteins and mapping of IgE epitopes","volume":"34","author":"S Saha","year":"2006","journal-title":"Nucleic acids research"},{"issue":"suppl_2","key":"pone.0310510.ref052","doi-asserted-by":"crossref","first-page":"W72","DOI":"10.1093\/nar\/gki396","article-title":"SCRATCH: a protein structure and structural feature prediction server","volume":"33","author":"J Cheng","year":"2005","journal-title":"Nucleic acids research"},{"issue":"6","key":"pone.0310510.ref053","first-page":"681","article-title":"SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments","volume":"11","author":"C Geourjon","year":"1995","journal-title":"Computer applications in the biosciences: CABIOS"},{"issue":"3","key":"pone.0310510.ref054","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":"C Combet","year":"2000","journal-title":"Trends in biochemical sciences"},{"issue":"2","key":"pone.0310510.ref055","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1006\/jmbi.1999.3091","article-title":"Protein secondary structure prediction based on position-specific scoring matrices","volume":"292","author":"DT Jones","year":"1999","journal-title":"Journal of molecular biology"},{"issue":"4","key":"pone.0310510.ref056","first-page":"404","article-title":"The PSIPRED protein structure prediction server","volume":"16","author":"LJ McGuffin","year":"2000","journal-title":"Bioinformatics (Oxford, England)"},{"key":"pone.0310510.ref057","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1741-7007-5-17","article-title":"Ab initio modeling of small proteins by iterative TASSER simulations","volume":"5","author":"S Wu","year":"2007","journal-title":"BMC biology"},{"key":"pone.0310510.ref058","doi-asserted-by":"crossref","first-page":"101169","DOI":"10.1016\/j.imu.2023.101169","article-title":"An in silico reverse vaccinology approach to design a novel multiepitope peptide vaccine for non-small cell lung cancers","volume":"37","author":"MM Rahman","year":"2023","journal-title":"Informatics in Medicine Unlocked"},{"issue":"Web Server issue","key":"pone.0310510.ref059","doi-asserted-by":"crossref","first-page":"W294","DOI":"10.1093\/nar\/gks493","article-title":"GalaxyWEB server for protein structure prediction and refinement","volume":"40","author":"J Ko","year":"2012","journal-title":"Nucleic acids research"},{"key":"pone.0310510.ref060","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: A program to check the stereochemical quality of protein structures","volume":"26","author":"R Laskowski","year":"1993","journal-title":"Journal of Applied Crystallography"},{"issue":"9","key":"pone.0310510.ref061","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1002\/pro.5560020916","article-title":"Verification of protein structures: patterns of nonbonded atomic interactions","volume":"2","author":"C Colovos","year":"1993","journal-title":"Protein science: a publication of the Protein Society"},{"issue":"5016","key":"pone.0310510.ref062","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1126\/science.1853201","article-title":"A method to identify protein sequences that fold into a known three-dimensional structure","volume":"253","author":"JU Bowie","year":"1991","journal-title":"Science (New York, NY)"},{"issue":"6364","key":"pone.0310510.ref063","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/356083a0","article-title":"Assessment of protein models with three-dimensional profiles","volume":"356","author":"R L\u00fcthy","year":"1992","journal-title":"Nature"},{"issue":"suppl_2","key":"pone.0310510.ref064","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":"M Wiederstein","year":"2007","journal-title":"Nucleic acids research"},{"issue":"W1","key":"pone.0310510.ref065","doi-asserted-by":"crossref","first-page":"W331","DOI":"10.1093\/nar\/gkz368","article-title":"Protein Interaction Z Score Assessment (PIZSA): an empirical scoring scheme for evaluation of protein-protein interactions","volume":"47","author":"AA Roy","year":"2019","journal-title":"Nucleic acids research"},{"key":"pone.0310510.ref066","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1186\/1471-2105-9-514","article-title":"ElliPro: a new structure-based tool for the prediction of antibody epitopes","volume":"9","author":"J Ponomarenko","year":"2008","journal-title":"BMC bioinformatics"},{"issue":"9","key":"pone.0310510.ref067","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1080\/00365540310015700","article-title":"Role of TLR4\/MD-2 and RP105\/MD-1 in innate recognition of lipopolysaccharide","volume":"35","author":"M Kimoto","year":"2003","journal-title":"Scandinavian journal of infectious diseases"},{"issue":"1","key":"pone.0310510.ref068","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1084\/jem.192.1.23","article-title":"The toll-like receptor protein RP105 regulates lipopolysaccharide signaling in B cells","volume":"192","author":"H Ogata","year":"2000","journal-title":"The Journal of experimental medicine"},{"issue":"1","key":"pone.0310510.ref069","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.chom.2008.12.002","article-title":"RP105 facilitates macrophage activation by Mycobacterium tuberculosis lipoproteins","volume":"5","author":"A Blumenthal","year":"2009","journal-title":"Cell host & microbe"},{"issue":"6","key":"pone.0310510.ref070","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/ni1198","article-title":"Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105","volume":"6","author":"S Divanovic","year":"2005","journal-title":"Nature Immunology"},{"issue":"1\u20132","key":"pone.0310510.ref071","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.vetimm.2005.07.012","article-title":"Bovine toll-like receptor 9: a comparative analysis of molecular structure, function and expression","volume":"108","author":"PJ Griebel","year":"2005","journal-title":"Veterinary immunology and immunopathology"},{"issue":"9","key":"pone.0310510.ref072","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.str.2020.06.006","article-title":"Performance and Its Limits in Rigid Body Protein-Protein Docking","volume":"28","author":"IT Desta","year":"2020","journal-title":"Structure (London, England: 1993)"},{"issue":"2","key":"pone.0310510.ref073","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nprot.2016.169","article-title":"The ClusPro web server for protein-protein docking","volume":"12","author":"D Kozakov","year":"2017","journal-title":"Nature protocols"},{"issue":"3","key":"pone.0310510.ref074","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/prot.25219","article-title":"New additions to the ClusPro server motivated by CAPRI","volume":"85","author":"S Vajda","year":"2017","journal-title":"Proteins"},{"issue":"7","key":"pone.0310510.ref075","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.1021\/acs.jcim.9b00105","article-title":"Using AMBER18 for Relative Free Energy Calculations","volume":"59","author":"LF Song","year":"2019","journal-title":"Journal of chemical information and modeling"},{"issue":"1","key":"pone.0310510.ref076","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1021\/acs.jctc.9b00591","article-title":"ff19SB: Amino-Acid-Specific Protein Backbone Parameters Trained against Quantum Mechanics Energy Surfaces in Solution","volume":"16","author":"C Tian","year":"2020","journal-title":"Journal of chemical theory and computation"},{"issue":"2","key":"pone.0310510.ref077","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1021\/acs.jcim.0c01390","article-title":"Parameterization of Monovalent Ions for the OPC3, OPC, TIP3P-FB, and TIP4P-FB Water Models","volume":"61","author":"A Sengupta","year":"2021","journal-title":"Journal of chemical information and modeling"},{"issue":"21","key":"pone.0310510.ref078","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1021\/jz501780a","article-title":"Building Water Models: A Different Approach","volume":"5","author":"S Izadi","year":"2014","journal-title":"The journal of physical chemistry letters"},{"issue":"52","key":"pone.0310510.ref079","doi-asserted-by":"crossref","first-page":"20749","DOI":"10.1073\/pnas.0709207104","article-title":"An extended dynamical hydration shell around proteins","volume":"104","author":"S Ebbinghaus","year":"2007","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"9","key":"pone.0310510.ref080","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.1021\/ct400314y","article-title":"Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 2. Explicit Solvent Particle Mesh Ewald","volume":"9","author":"R Salomon-Ferrer","year":"2013","journal-title":"Journal of chemical theory and computation"},{"issue":"5","key":"pone.0310510.ref081","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1021\/ct200909j","article-title":"Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 1. Generalized Born","volume":"8","author":"AW G\u00f6tz","year":"2012","journal-title":"Journal of chemical theory and computation"},{"issue":"9","key":"pone.0310510.ref082","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/ct300418h","article-title":"MMPBSA.py: An Efficient Program for End-State Free Energy Calculations","volume":"8","author":"BR Miller","year":"2012","journal-title":"Journal of chemical theory and computation"},{"issue":"1","key":"pone.0310510.ref083","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1021\/ci100275a","article-title":"Assessing the performance of the MM\/PBSA and MM\/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations","volume":"51","author":"T Hou","year":"2011","journal-title":"Journal of chemical information and modeling"},{"issue":"31","key":"pone.0310510.ref084","doi-asserted-by":"crossref","first-page":"16719","DOI":"10.1039\/C4CP01388C","article-title":"Assessing the performance of MM\/PBSA and MM\/GBSA methods. 4. Accuracies of MM\/PBSA and MM\/GBSA methodologies evaluated by various simulation protocols using PDBbind data set","volume":"16","author":"H Sun","year":"2014","journal-title":"Physical chemistry chemical physics: PCCP"},{"issue":"9","key":"pone.0310510.ref085","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1261\/rna.065896.118","article-title":"Assessing the performance of MM\/PBSA and MM\/GBSA methods. 8. Predicting binding free energies and poses of protein-RNA complexes","volume":"24","author":"F Chen","year":"2018","journal-title":"RNA (New York, NY)"},{"issue":"W1","key":"pone.0310510.ref086","doi-asserted-by":"crossref","first-page":"W322","DOI":"10.1093\/nar\/gkz397","article-title":"HawkDock: a web server to predict and analyze the protein\u2013protein complex based on computational docking and MM\/GBSA","volume":"47","author":"G Weng","year":"2019","journal-title":"Nucleic acids research"},{"issue":"42","key":"pone.0310510.ref087","doi-asserted-by":"crossref","first-page":"423202","DOI":"10.1088\/0953-8984\/22\/42\/423202","article-title":"Normal mode analysis and applications in biological physics","volume":"22","author":"EC Dykeman","year":"2010","journal-title":"Journal of physics Condensed matter: an Institute of Physics journal"},{"issue":"Web Server issue","key":"pone.0310510.ref088","doi-asserted-by":"crossref","first-page":"W271","DOI":"10.1093\/nar\/gku339","article-title":"iMODS: internal coordinates normal mode analysis server","volume":"42","author":"JR L\u00f3pez-Blanco","year":"2014","journal-title":"Nucleic acids research"},{"issue":"1","key":"pone.0310510.ref089","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1038\/s41598-020-80899-6","article-title":"In silico analysis of epitope-based vaccine candidate against tuberculosis using reverse vaccinology","volume":"11","author":"S Bibi","year":"2021","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0310510.ref090","doi-asserted-by":"crossref","first-page":"9232","DOI":"10.1038\/s41598-017-09199-w","article-title":"Exploring dengue genome to construct a multi-epitope based subunit vaccine by utilizing immunoinformatics approach to battle against dengue infection","volume":"7","author":"M Ali","year":"2017","journal-title":"Sci Rep"},{"issue":"4","key":"pone.0310510.ref091","doi-asserted-by":"crossref","first-page":"e9862","DOI":"10.1371\/journal.pone.0009862","article-title":"Computational Immunology Meets Bioinformatics: The Use of Prediction Tools for Molecular Binding in the Simulation of the Immune System","volume":"5","author":"N Rapin","year":"2010","journal-title":"PLOS ONE"},{"key":"pone.0310510.ref092","first-page":"2013","article-title":"Immune System Simulation Online","volume":"27","author":"N Rapin","year":"2011","journal-title":"Bioinformatics (Oxford, England)"},{"issue":"Database issue","key":"pone.0310510.ref093","doi-asserted-by":"crossref","first-page":"D670","DOI":"10.1093\/nar\/gku1177","article-title":"The UCSC Genome Browser database: 2015 update","volume":"43","author":"KR Rosenbloom","year":"2015","journal-title":"Nucleic acids research"},{"issue":"2","key":"pone.0310510.ref094","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.sjbs.2021.09.061","article-title":"Prediction and evaluation of multi epitope based sub-unit vaccine against Salmonella typhimurium","volume":"29","author":"S Zafar","year":"2022","journal-title":"Saudi journal of biological sciences"},{"key":"pone.0310510.ref095","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.meegid.2017.04.009","article-title":"Development of a multi-epitope peptide vaccine inducing robust T cell responses against brucellosis using immunoinformatics based approaches","volume":"51","author":"M Saadi","year":"2017","journal-title":"Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases"},{"issue":"1","key":"pone.0310510.ref096","first-page":"323","article-title":"In silico Analysis of a 29 kDa Echinococcus granulosus Protoscolex Protein (P29) as a Vaccine Candidate against Cystic Echinococcosis","volume":"78","author":"S Khazaei","year":"2023","journal-title":"Archives of Razi Institute"},{"issue":"3","key":"pone.0310510.ref097","doi-asserted-by":"crossref","first-page":"131","DOI":"10.15171\/bi.2019.18","article-title":"A multi-method and structure-based in silico vaccine designing against Echinococcus granulosus through investigating enolase protein","volume":"9","author":"MM Pourseif","year":"2019","journal-title":"BioImpacts: BI"},{"key":"pone.0310510.ref098","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2147\/ITT.S241064","article-title":"Immunoinformatics and Vaccine Development: An Overview","volume":"9","author":"AN Oli","year":"2020","journal-title":"ImmunoTargets and therapy"},{"key":"pone.0310510.ref099","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/978-981-16-8969-7_5","volume-title":"Translational Informatics: Prevention and Treatment of Viral Infections","author":"S Joon","year":"2022"},{"issue":"9","key":"pone.0310510.ref100","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/j.1365-3024.1996.tb01029.x","article-title":"Vaccination against hydatidosis using a defined recombinant antigen","volume":"18","author":"MW Lightowlers","year":"1996","journal-title":"Parasite immunology"},{"issue":"3","key":"pone.0310510.ref101","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1111\/tbed.13772","article-title":"Current situation and future prospects of Echinococcus granulosus vaccine candidates: A systematic review","volume":"68","author":"D Anvari","year":"2021","journal-title":"Transboundary and emerging diseases"},{"issue":"4","key":"pone.0310510.ref102","doi-asserted-by":"crossref","first-page":"e5362","DOI":"10.1371\/journal.pone.0005362","article-title":"The EG95 Antigen of Echinococcus spp. Contains Positively Selected Amino Acids, which May Influence Host Specificity and Vaccine Efficacy","volume":"4","author":"KL Haag","year":"2009","journal-title":"PLOS ONE"},{"issue":"3","key":"pone.0310510.ref103","doi-asserted-by":"crossref","first-page":"657","DOI":"10.3892\/etm.2013.1187","article-title":"The prediction of T- and B-combined epitope and tertiary structure of the Eg95 antigen of Echinococcus granulosus","volume":"6","author":"X Ma","year":"2013","journal-title":"Experimental and therapeutic medicine"},{"issue":"1","key":"pone.0310510.ref104","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s42003-022-03125-1","article-title":"Chromosome-scale Echinococcus granulosus (genotype G1) genome reveals the Eg95 gene family and conservation of the EG95-vaccine molecule","volume":"5","author":"PK Korhonen","year":"2022","journal-title":"Communications Biology"},{"issue":"Pt 1","key":"pone.0310510.ref105","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1042\/bj20021402","article-title":"Echinococcus granulosus antigen 5 is closely related to proteases of the trypsin family","volume":"369","author":"C Lorenzo","year":"2003","journal-title":"The Biochemical journal"},{"issue":"11","key":"pone.0310510.ref106","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1016\/j.celrep.2019.11.034","article-title":"Compromised Metabolic Reprogramming Is an Early Indicator of CD8(+) T Cell Dysfunction during Chronic Mycobacterium tuberculosis Infection","volume":"29","author":"SL Russell","year":"2019","journal-title":"Cell reports"},{"issue":"1","key":"pone.0310510.ref107","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/s41385-019-0217-6","article-title":"Limited recognition of Mycobacterium tuberculosis-infected macrophages by polyclonal CD4 and CD8 T cells from the lungs of infected mice","volume":"13","author":"YR Patankar","year":"2020","journal-title":"Mucosal immunology"},{"issue":"9","key":"pone.0310510.ref108","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1128\/JB.185.9.2692-2699.2003","article-title":"Thirteen years of building constraint-based in silico models of Escherichia coli","volume":"185","author":"JL Reed","year":"2003","journal-title":"Journal of bacteriology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0310510","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T18:27:27Z","timestamp":1739384847000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0310510"}},"subtitle":[],"editor":[{"given":"Asma","family":"Haque","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,2,12]]},"references-count":108,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0310510","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,12]]}}}