{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:57:52Z","timestamp":1760709472903,"version":"3.41.2"},"reference-count":92,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T00:00:00Z","timestamp":1513036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Molecular Recognition"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>With the development of de novo binders for protein targets from non\u2010related scaffolds, many possibilities for therapeutics and diagnostics have been created. In this study, we described the use of de novo design approach to create single\u2010chain fragment variable (scFv) for <jats:italic>Salmonella enterica<\/jats:italic> subspecies <jats:italic>enterica<\/jats:italic> serovar Typhi TolC protein. Typhoid fever is a global health concern in developing and underdeveloped countries. Rapid typhoid diagnostics will improve disease management and therapy. In this work, molecular dynamics simulation was first performed on a homology model of TolC protein in POPE membrane bilayer to obtain the central structure that was subsequently used as the target for scFv design. Potential hotspot residues capable of anchoring the binders to the target were identified by docking \u201cdisembodied\u201d amino acid residues against TolC surface. Next, scFv scaffolds were selected from Protein Data Bank to harbor the computed hotspot residues. The hotspot residues were then incorporated into the scFv scaffold complementarity determining regions. The designs recapitulated binding energy, shape complementarity, and interface surface area of natural protein\u2010antibody interfaces. This approach has yielded 5 designs with high binding affinity against TolC that may be beneficial for the future development of antigen\u2010based detection agents for typhoid diagnostics.<\/jats:p>","DOI":"10.1002\/jmr.2695","type":"journal-article","created":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T05:54:43Z","timestamp":1513058083000},"source":"Crossref","is-referenced-by-count":6,"title":["Integration of molecular dynamics simulation and hotspot residues grafting for de novo scFv design against <i>Salmonella<\/i> Typhi TolC protein"],"prefix":"10.1002","volume":"31","author":[{"given":"Siew Wen","family":"Leong","sequence":"first","affiliation":[{"name":"Institute for Research in Molecular Medicine (INFORMM) Universiti Sains Malaysia  Minden Penang Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theam Soon","family":"Lim","sequence":"additional","affiliation":[{"name":"Institute for Research in Molecular Medicine (INFORMM) Universiti Sains Malaysia  Minden Penang Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asma","family":"Ismail","sequence":"additional","affiliation":[{"name":"Institute for Research in Molecular Medicine (INFORMM) Universiti Sains Malaysia, Health Campus  Kubang Kerian Kelantan Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5067-2073","authenticated-orcid":false,"given":"Yee Siew","family":"Choong","sequence":"additional","affiliation":[{"name":"Institute for Research in Molecular Medicine (INFORMM) Universiti Sains Malaysia  Minden Penang Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,12,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2013.10.008"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0409-331"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.20776"},{"issue":"9","key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"12547","DOI":"10.1007\/s13277-016-5105-z","article-title":"In silico designing, cloning, and heterologous expression of novel chimeric human B lymphocyte CD20 extra loop","volume":"37","author":"Fasihi\u2010Ramandi M","year":"2016","journal-title":"Tumour Biol"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087099"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/978-1-4939-6637-0_21","article-title":"Computational tools for aiding rational antibody design","volume":"1529","author":"Krawczyk K","year":"2016","journal-title":"Methods Mol Biol"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzs024"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105954"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2011.10.026"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2014.07.006"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-bioeng-071114-040733"},{"issue":"5","key":"e_1_2_8_13_1","first-page":"346","article-title":"The global burden of typhoid fever","volume":"82","author":"Crump JA","year":"2004","journal-title":"Bull World Health Organ"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1086\/649541"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis025"},{"issue":"2","key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1995-7645(13)60017-6","article-title":"Outbreak of Salmonella typhi enteric fever in sub\u2010urban area of North India: a public health perspective","volume":"6","author":"Singla N","year":"2013","journal-title":"Asian Pac J Trop Med"},{"issue":"2","key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"256","DOI":"10.5455\/ijmsph.2015.0000201448","article-title":"An outbreak investigation of typhoid fever in Pondicherry, South India, 2013","volume":"4","author":"Cherian J","year":"2015","journal-title":"Int J Med Sci Public Health"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0111768"},{"issue":"8","key":"e_1_2_8_19_1","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1093\/cid\/cis012","article-title":"Multidrug\u2010resistant typhoid fever with neurologic findings on the Malawi\u2010Mozambique border","volume":"54","author":"Lutterloh E","year":"2012","journal-title":"Clin Infect Dis"},{"key":"e_1_2_8_20_1","first-page":"49","article-title":"Typhoid vaccines: WHO position paper","volume":"83","author":"WHO","year":"2008","journal-title":"Wkly Epidemiol Rec"},{"key":"e_1_2_8_21_1","first-page":"35","article-title":"Recent advancement in typhoid research\u2014a review","volume":"7","author":"Khan KH","year":"2008","journal-title":"Advanced Biotech"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020201"},{"issue":"9","key":"e_1_2_8_23_1","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1128\/jcm.26.9.1824-1830.1988","article-title":"Detection with monoclonal antibody of Salmonella typhi antigen 9 in specimens from patients","volume":"26","author":"Chaicumpa W","year":"1988","journal-title":"J Clin Microbiol"},{"key":"e_1_2_8_24_1","first-page":"205","article-title":"Diagnosis of enteric fever caused by Salmonella spp. in Vietnam by a monoclonal antibody\u2010based dot\u2010blot ELISA. Asian Pac. J","volume":"15","author":"Quang NN","year":"1997","journal-title":"Allerg Immunol"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2011.01.008"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402230200"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.09.001"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-177-2_8"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2006.08.006"},{"issue":"3","key":"e_1_2_8_30_1","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1128\/mr.42.3.614-659.1978","article-title":"Enzymology, genetics, and regulation of membrane phospholipid synthesis in Escherichia coli","volume":"42","author":"Raetz CR","year":"1978","journal-title":"Microbiol Rev"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(96)00018-5"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20291"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.105.078154"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp973084f"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp101759q"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.2408420"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.328693"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevA.31.1695"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/00268978400101201"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-3773(19990115)38:1\/2<236::AID-ANIE236>3.0.CO;2-M"},{"issue":"3","key":"e_1_2_8_42_1","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.bbapap.2011.12.007","article-title":"Antigen\u2010antibody interface properties: composition, residue interactions and features of 53 non\u2010redundant structures","volume":"1824","author":"Ramaraj T","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024657"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(03)00670-3"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.074"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560060807"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1997.0959"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020044"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707977104"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1190239"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.03.010"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104364200"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.08.019"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.051520605"},{"issue":"3","key":"e_1_2_8_55_1","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1021\/bc060203y","article-title":"A human antibody fragment with high affinity for biodegradable polymer film","volume":"18","author":"Watanabe H","year":"2007","journal-title":"Bioconjug Chem"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603275200"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.238410"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601744"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.255"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-45784-4_14"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1202617"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks480"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1993.1648"},{"key":"e_1_2_8_64_1","unstructured":"Accelrys Software Inc. Discovery studio modeling environment.2013: San Diego."},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.108.136028"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/35016007"},{"volume-title":"Advances in Protein Chemistry","year":"2002","author":"Sundberg EJ","key":"e_1_2_8_67_1"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986709787581914"},{"volume-title":"Computational Protein Design, in The PhD School of Science","year":"2012","author":"Johansson K","key":"e_1_2_8_69_1"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-S14-S6"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201110679"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biophys.36.040306.132643"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi201814s"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.23143"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2009.12.007"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fob.2014.04.011"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-0285.2011.01101.x"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2013.06.035"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1089427"},{"issue":"12","key":"e_1_2_8_80_1","doi-asserted-by":"crossref","first-page":"4776","DOI":"10.1073\/pnas.87.12.4776","article-title":"TolC, an Escherichia coli outer membrane protein required for hemolysin secretion","volume":"87","author":"Wandersman C","year":"1990","journal-title":"Proc Natl Acad Sci U S A"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811070106"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2008.09.012"},{"key":"e_1_2_8_83_1","first-page":"e50476","article-title":"Protein WISDOM: a workbench for in silico de novo design of biomolecules","author":"Smadbeck J","year":"2013","journal-title":"J Vis Exp"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl163"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzq061"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2010.09.050"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.09.023"},{"key":"e_1_2_8_88_1","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1021\/bi100978r","article-title":"Computational design and biophysical characterization of aggregation\u2010resistant point mutations for \u03b3D crystallin illustrate a balance of conformational stability and intrinsic aggregation propensity","volume":"50","author":"Sahin E","year":"2010","journal-title":"Biochemistry"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2010.10.002"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.enzmictec.2010.04.003"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar900273t"},{"issue":"4","key":"e_1_2_8_92_1","first-page":"563","article-title":"Dot enzyme immunosorbent assay for the serodiagnosis of typhoid fever","volume":"22","author":"Ismail A","year":"1991","journal-title":"Southeast Asian J Trop Med Public Health"},{"issue":"1","key":"e_1_2_8_93_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0006-291X(05)81417-2","article-title":"Demonstration of an antigenic protein specific for Salmonella typhi","volume":"181","author":"Ismail A","year":"1991","journal-title":"Biochem Biophys Res Commun"}],"container-title":["Journal of Molecular Recognition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjmr.2695","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmr.2695","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T16:04:50Z","timestamp":1695571490000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmr.2695"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,12]]},"references-count":92,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1002\/jmr.2695"],"URL":"https:\/\/doi.org\/10.1002\/jmr.2695","archive":["Portico"],"relation":{},"ISSN":["0952-3499","1099-1352"],"issn-type":[{"type":"print","value":"0952-3499"},{"type":"electronic","value":"1099-1352"}],"subject":[],"published":{"date-parts":[[2017,12,12]]},"article-number":"e2695"}}