{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T07:43:47Z","timestamp":1781077427187,"version":"3.54.1"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2013,7,4]],"date-time":"2013-07-04T00:00:00Z","timestamp":1372896000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1003127","type":"journal-article","created":{"date-parts":[[2013,7,4]],"date-time":"2013-07-04T22:28:59Z","timestamp":1372976939000},"page":"e1003127","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Pathway-based Screening Strategy for Multitarget Inhibitors of Diverse Proteins in Metabolic Pathways"],"prefix":"10.1371","volume":"9","author":[{"given":"Kai-Cheng","family":"Hsu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chi","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Fu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Ching","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinn-Moon","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,7,4]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/nrd1086","article-title":"Hit and lead generation: Beyond high-throughput screening","volume":"2","author":"KH Bleicher","year":"2003","journal-title":"Nat Rev Drug Discov"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/S1359-6446(02)02483-2","article-title":"Structure-based virtual screening: an overview","volume":"7","author":"PD Lyne","year":"2002","journal-title":"Drug Discov Today"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/nrd1549","article-title":"Docking and scoring in virtual screening for drug discovery: methods and applications","volume":"3","author":"DB Kitchen","year":"2004","journal-title":"Nature Reviews Drug Discovery"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S1367-5931(02)00339-3","article-title":"Lead discovery using molecular docking","volume":"6","author":"BK Shoichet","year":"2002","journal-title":"Current Opinion in Chemical Biology"},{"key":"ref5","first-page":"194","article-title":"Structure-based virtual screening of chemical libraries for drug discovery Current Opinion in Chemical","volume":"10","author":"S Ghosh","year":"2006","journal-title":"Biology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1056\/NEJMp058291","article-title":"Oseltamivir resistance - disabling our influenza defenses","volume":"353","author":"A Moscona","year":"2005","journal-title":"N Engl J Med"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1128\/JVI.78.7.3722-3732.2004","article-title":"Positive selection detection in 40,000 human immunodeficiency virus (HIV) type 1 sequences automatically identifies drug resistance and positive fitness mutations in HIV protease and reverse transcriptase","volume":"78","author":"LM Chen","year":"2004","journal-title":"Journal of Virology"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/nrd2759","article-title":"Double-edged swords as cancer therapeutics: simultaneously targeting p53 and NF-kappa B pathways","volume":"7","author":"A Dey","year":"2008","journal-title":"Nat Rev Drug Discov"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/nrc2787","article-title":"Targeting the cancer kinome through polypharmacology","volume":"10","author":"ZA Knight","year":"2010","journal-title":"Nat Rev Cancer"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.tips.2007.11.007","article-title":"Novel paradigms for drug discovery: computational multitarget screening","volume":"29","author":"E Jenwitheesuk","year":"2008","journal-title":"Trends Pharmacol Sci"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1126\/science.1174671","article-title":"Three-dimensional structural view of the central metabolic network of Thermotoga maritima","volume":"325","author":"Y Zhang","year":"2009","journal-title":"Science"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1146\/annurev.mi.30.100176.002205","article-title":"Enzyme recruitment in evolution of new function","volume":"30","author":"RA Jensen","year":"1976","journal-title":"Annu Rev Microbiol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"W424","DOI":"10.1093\/nar\/gkq480","article-title":"SiMMap: a web server for inferring site-moiety map to recognize interaction preferences between protein pockets and compound moieties","volume":"38","author":"YF Chen","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"e32142","DOI":"10.1371\/journal.pone.0032142","article-title":"Core site-moiety maps reveal inhibitors and binding mechanisms of orthologous proteins by screening compound libraries","volume":"7","author":"KC Hsu","year":"2012","journal-title":"PLoS One"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/41483","article-title":"The complete genome sequence of the gastric pathogen Helicobacter pylori","volume":"388","author":"JF Tomb","year":"1997","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/16495","article-title":"Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori","volume":"397","author":"RA Alm","year":"1999","journal-title":"Nature"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/30718","article-title":"Evidence for the shikimate pathway in apicomplexan parasites","volume":"393","author":"F Roberts","year":"1998","journal-title":"Nature"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"4682","DOI":"10.1111\/j.1742-4658.2006.05469.x","article-title":"Biochemical characterization and inhibitor discovery of shikimate dehydrogenase from Helicobacter pylori","volume":"273","author":"C Han","year":"2006","journal-title":"FEBS J"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"8156","DOI":"10.1128\/JB.187.23.8156-8163.2005","article-title":"Structural basis for shikimate-binding specificity of Helicobacter pylori shikimate kinase","volume":"187","author":"WC Cheng","year":"2005","journal-title":"J Bacteriol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/prot.20035","article-title":"GEMDOCK: a generic evolutionary method for molecular docking","volume":"55","author":"JM Yang","year":"2004","journal-title":"Proteins: Structure, Function, and Bioinformatics"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1023\/A:1011115820450","article-title":"DOCK 4.0: search strategies for automated molecular docking of flexible molecule databases","volume":"15","author":"TJ Ewing","year":"2001","journal-title":"J Comput Aided Mol Des"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1002\/(SICI)1097-0134(19991101)37:2<228::AID-PROT8>3.0.CO;2-8","article-title":"Evaluation of the FLEXX incremental construction algorithm for protein-ligand docking","volume":"37","author":"B Kramer","year":"1999","journal-title":"Proteins"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1006\/jmbi.1996.0897","article-title":"Development and validation of a genetic algorithm for flexible docking","volume":"267","author":"G Jones","year":"1997","journal-title":"J Mol Biol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/prot.20387","article-title":"A pharmacophore-based evolutionary approach for screening selective estrogen receptor modulators","volume":"59","author":"JM Yang","year":"2005","journal-title":"Proteins-Structure Function and Bioinformatics"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"e428","DOI":"10.1371\/journal.pone.0000428","article-title":"Combinatorial computational approaches to identify tetracycline derivatives as flavivirus inhibitors","volume":"2","author":"JM Yang","year":"2007","journal-title":"PLoS One"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.jmb.2009.11.076","article-title":"The cAMP receptor-like protein CLP is a novel c-di-GMP receptor linking cell-cell signaling to virulence gene expression in Xanthomonas campestris","volume":"396","author":"KH Chin","year":"2010","journal-title":"J Mol Biol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"4268","DOI":"10.1021\/cg800697s","article-title":"Rational design for crystallization of beta-lactoglobulin and vitamin D-3 complex: revealing a secondary binding site","volume":"8","author":"MC Yang","year":"2008","journal-title":"Cryst Growth Des"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.jmb.2007.08.017","article-title":"Crystal structures of shikimate dehydrogenase AroE from Thermus thermophilus HB8 and its cofactor and substrate complexes: Insights into the enzymatic mechanism","volume":"373","author":"B Bagautdinov","year":"2007","journal-title":"J Mol Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.jmb.2006.09.001","article-title":"Mechanism of phosphoryl transfer catalyzed by shikimate kinase from Mycobacterium tuberculosis","volume":"364","author":"MD Hartmann","year":"2006","journal-title":"J Mol Biol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"7162","DOI":"10.1074\/jbc.M412028200","article-title":"Site-directed mutagenesis of the active site region in the quinate\/shikimate 5-dehydrogenase YdiB of Escherichia coli","volume":"280","author":"HA Lindner","year":"2005","journal-title":"J Biol Chem"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"e33481","DOI":"10.1371\/journal.pone.0033481","article-title":"Structures of Helicobacter pylori shikimate kinase reveal a selective inhibitor-induced-fit mechanism","volume":"One7","author":"WC Cheng","year":"2012","journal-title":"PLoS"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"W299","DOI":"10.1093\/nar\/gki370","article-title":"ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures","volume":"33","author":"M Landau","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"14295","DOI":"10.1073\/pnas.97.26.14295","article-title":"Explaining the high mutation rates of cancer cells to drug and multidrug resistance by chromosome reassortments that are catalyzed by aneuploidy","volume":"97","author":"P Duesberg","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1126\/science.7038875","article-title":"Variation of Influenza-A, Influenza-B, and Influenza-C viruses","volume":"215","author":"P Palese","year":"1982","journal-title":"Science"},{"key":"ref35","first-page":"1020","article-title":"Drug evaluation: VX-702, a MAP kinase inhibitor for rheumatoid arthritis and acute coronary syndrome","volume":"7","author":"CH Ding","year":"2006","journal-title":"Curr Opin Investig Drugs"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"W152","DOI":"10.1093\/nar\/gkl187","article-title":"(PS)(2): protein structure prediction server","volume":"34","author":"CC Chen","year":"2006","journal-title":"Nucleic Acids Research"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/28431","article-title":"Structure of dehydroquinate synthase reveals an active site capable of multistep catalysis","volume":"394","author":"EP Carpenter","year":"1998","journal-title":"Nature"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1093\/protein\/11.9.739","article-title":"Protein structure alignment by incremental combinatorial extension (CE) of the optimal path","volume":"11","author":"IN Shindyalov","year":"1998","journal-title":"Protein Eng"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"8539","DOI":"10.1021\/bi0606290","article-title":"Crystal structure of Mycobacterium tuberculosis shikimate kinase in complex with shikimic acid and an ATP analogue","volume":"45","author":"JH Gan","year":"2006","journal-title":"Biochemistry"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T19:14:35Z","timestamp":1539976475000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003127"}},"subtitle":[],"editor":[{"given":"Costas D.","family":"Maranas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,7,4]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2013,7,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1003127","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,4]]}}}