{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:45:10Z","timestamp":1791823510045,"version":"4.3.4"},"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2009,10,26]],"date-time":"2009-10-26T00:00:00Z","timestamp":1256515200000},"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.1000530","type":"journal-article","created":{"date-parts":[[2009,10,26]],"date-time":"2009-10-26T15:19:23Z","timestamp":1256570363000},"page":"e1000530","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":32,"title":["The Role of Medical Structural Genomics in Discovering New Drugs for Infectious Diseases"],"prefix":"10.1371","volume":"5","author":[{"given":"Wesley C.","family":"Van Voorhis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim G. J.","family":"Hol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Myler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance J.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2009,10,26]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nrd2201","article-title":"Drugs for bad bugs: Confronting the challenges of antibacterial discovery.","volume":"6","author":"DJ Payne","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-1-60327-058-8_4","article-title":"Data management in structural genomics: An overview.","volume":"426","author":"S Haquin","year":"2008","journal-title":"Methods Mol Biol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.mib.2007.07.001","article-title":"Antibacterial targets in fatty acid biosynthesis.","volume":"10","author":"HT Wright","year":"2007","journal-title":"Curr Opin Microbiol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nature07772","article-title":"Type II fatty acid synthesis is not a suitable antibiotic target for gram-positive pathogens.","volume":"458","author":"S Brinster","year":"2009","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nchembio.100","article-title":"An integrated platform of genomic assays reveals small-molecule bioactivities.","volume":"4","author":"S Hoon","year":"2008","journal-title":"Nat Chem Biol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.ab.2006.07.027","article-title":"Thermofluor-based high-throughput stability optimization of proteins for structural studies.","volume":"357","author":"UB Ericsson","year":"2006","journal-title":"Anal Biochem"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"3661","DOI":"10.1021\/jm8000373","article-title":"Recent developments in fragment-based drug discovery.","volume":"51","author":"M Congreve","year":"2008","journal-title":"J Med Chem"},{"key":"ref8","first-page":"365","article-title":"Antitrypanosomiasis drug development based on structures of glycolytic enzymes.","author":"CLMJ Verlinde","year":"1997"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nrd1467","article-title":"Fragment-based lead discovery.","volume":"3","author":"DC Rees","year":"2004","journal-title":"Nat Rev Drug Discov"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/S1359-6446(03)02831-9","article-title":"A \u201crule of three\u201d for fragment-based lead discovery?","volume":"8","author":"M Congreve","year":"2003","journal-title":"Drug Discov Today"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1038\/80319","article-title":"Discovering novel ligands for macromolecules using X-ray crystallographic screening.","volume":"18","author":"VL Nienaber","year":"2000","journal-title":"Nature Biotechnol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.2174\/156802607782341073","article-title":"SPR-based fragment screening: Advantages and applications.","volume":"7","author":"T Neumann","year":"2007","journal-title":"Curr Top Med Chem"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.cbpa.2007.07.010","article-title":"Fragment-based screening using X-ray crystallography and NMR spectroscopy.","volume":"11","author":"H Jhoti","year":"2007","journal-title":"Curr Opin Chem Biol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.copbio.2006.10.007","article-title":"Fragment-based lead discovery: A chemical update.","volume":"17","author":"DA Erlanson","year":"2006","journal-title":"Curr Opin Biotechnol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"5939","DOI":"10.1021\/jm060429m","article-title":"Using fragment cocktail crystallography to assist inhibitor design of <italic>Trypanosoma brucei<\/italic> nucleoside 2-deoxyribosyltransferase.","volume":"49","author":"J Bosch","year":"2006","journal-title":"J Med Chem"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"4694","DOI":"10.1021\/jm900259h","article-title":"Discovery of leukotriene A4 hydrolase inhibitors using metabolomics biased fragment crystallography.","volume":"52","author":"DR Davies","year":"2009","journal-title":"J Med Chem"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/372695a0","article-title":"A potent peptidomimetic inhibitor of HSV ribonucleotide reductase with antiviral activity in vivo.","volume":"372","author":"M Liuzzi","year":"1994","journal-title":"Nature"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/nature06526","article-title":"Reaching for high-hanging fruit in drug discovery at protein-protein interfaces.","volume":"450","author":"JA Wells","year":"2007","journal-title":"Nature"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1107\/S0907444996000376","article-title":"Structure of <italic>Escherichia coli<\/italic> inorganic pyrophosphatase at 2.2 \u00c5 resolution.","volume":"52","author":"J Kankare","year":"1996","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1021\/bi0619977","article-title":"A complete structural description of the catalytic cycle of yeast pyrophosphatase.","volume":"46","author":"E Oksanen","year":"2007","journal-title":"Biochemistry"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0014-5793(99)00779-6","article-title":"Evolutionary aspects of inorganic pyrophosphatase.","volume":"454","author":"T Sivula","year":"1999","journal-title":"FEBS Lett"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.chembiol.2008.04.012","article-title":"Shape shifting leads to small-molecule allosteric drug discovery.","volume":"15","author":"SH Lawrence","year":"2008","journal-title":"Chem Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"D301","DOI":"10.1093\/nar\/gkl971","article-title":"The worldwide Protein Data Bank (wwPDB): Ensuring a single, uniform archive of PDB data.","volume":"35","author":"H Berman","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nchembio0709-436","article-title":"Open access chemical and clinical probes to support drug discovery.","volume":"5","author":"AM Edwards","year":"2009","journal-title":"Nat Chem Biol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1110\/ps.04872204","article-title":"Design, expression, and purification of a Flaviviridae polymerase using a high-throughput approach to facilitate crystal structure determination.","volume":"13","author":"KH Choi","year":"2004","journal-title":"Protein Sci"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.pep.2007.11.008","article-title":"The use of systematic N- and C-terminal deletions to promote production and structural studies of recombinant proteins.","volume":"58","author":"S Graslund","year":"2008","journal-title":"Protein Expr Purif"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/S1047-8477(03)00048-0","article-title":"A deliberate approach to screening for initial crystallization conditions of biological macromolecules.","volume":"142","author":"JR Luft","year":"2003","journal-title":"J Struct Biol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1107\/S0021889802001474","article-title":"An approach to rapid protein crystallization using nanodroplets.","volume":"35","author":"BDYD Santarsiero","year":"2002","journal-title":"J Appl Crystallogr"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"16531","DOI":"10.1073\/pnas.262485199","article-title":"A robust and scalable microfluidic metering method that allows protein crystal growth by free interface diffusion.","volume":"99","author":"CL Hansen","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"11170","DOI":"10.1021\/ja037166v","article-title":"Screening of protein crystallization conditions on a microfluidic chip using nanoliter-size droplets.","volume":"125","author":"B Zheng","year":"2003","journal-title":"J Am Chem Soc"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1107\/S0907444908028060","article-title":"The plug-based nanovolume Microcapillary Protein Crystallization System (MPCS).","volume":"64","author":"CJ Gerdts","year":"2008","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1107\/S0907444902016633","article-title":"Towards the automated evaluation of crystallization trials.","volume":"58","author":"J Wilson","year":"2002","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1107\/S0907444905041648","article-title":"Automated classification of protein crystallization images using support vector machines with scale-invariant texture and Gabor features.","volume":"62","author":"S Pan","year":"2006","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1107\/S090744490802982X","article-title":"Image-based crystal detection: A machine-learning approach.","volume":"64","author":"R Liu","year":"2008","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/978-1-60327-058-8_33","article-title":"Structural genomics of pathogenic protozoa: An overview.","volume":"426","author":"E Fan","year":"2008","journal-title":"Methods Mol Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1002\/prot.22213","article-title":"Crystal structure of ultralente\u2014A microcrystalline insulin suspension.","volume":"74","author":"A Wagner","year":"2009","journal-title":"Proteins"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1107\/S0021889803018375","article-title":"Microfabricated mounts for high-throughput macromolecular cryocrystallography.","volume":"36","author":"RESZ Thorne","year":"2003","journal-title":"J Applied Crystallography"},{"key":"ref38","first-page":"157","article-title":"Studies on the mechanisms of action of the immunomodulator Bestatin in various screening test systems.","author":"HU Schorlemmer","year":"1984","journal-title":"Behring Inst Mitt:"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2174\/092986706775197999","article-title":"Privileged structures as leads in medicinal chemistry.","volume":"13","author":"L Costantino","year":"2006","journal-title":"Curr Med Chem"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"4641","DOI":"10.1016\/j.bmcl.2007.05.075","article-title":"Heterocyclic alpha-helix mimetics for targeting protein-protein interactions.","volume":"17","author":"SM Biros","year":"2007","journal-title":"Bioorg Med Chem Lett"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1021\/ar700259k","article-title":"Beta-hairpin peptidomimetics: design, structures and biological activities.","volume":"41","author":"JA Robinson","year":"2008","journal-title":"Acc Chem Res"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1042\/BST0361414","article-title":"alpha-Helix mimetics as inhibitors of protein-protein interactions.","volume":"36","author":"I Saraogi","year":"2008","journal-title":"Biochem Soc Trans"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.2174\/1381612043384448","article-title":"HIV-1 gp41 as a target for viral entry inhibition.","volume":"10","author":"MJ Root","year":"2004","journal-title":"Curr Pharm Des"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/387426a0","article-title":"Atomic structure of the ectodomain from HIV-1 gp41.","volume":"387","author":"W Weissenhorn","year":"1997","journal-title":"Nature"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/13324","article-title":"Selection of gp41-mediated HIV-1 cell entry inhibitors from biased combinatorial libraries of non-natural binding elements.","volume":"6","author":"M Ferrer","year":"1999","journal-title":"Nat Struct Biol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/342299a0","article-title":"X-ray analysis of HIV-1 proteinase at 2.7 \u00c5 resolution confirms structural homology among retroviral enzymes.","volume":"342","author":"R Lapatto","year":"1989","journal-title":"Nature"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1126\/science.2686029","article-title":"Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 \u00c5 resolution.","volume":"246","author":"M Miller","year":"1989","journal-title":"Science"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/337615a0","article-title":"Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1.","volume":"337","author":"MA Navia","year":"1989","journal-title":"Nature"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1126\/science.2548279","article-title":"Conserved folding in retroviral proteases: Crystal structure of a synthetic HIV-1 protease.","volume":"245","author":"A Wlodawer","year":"1989","journal-title":"Science"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1146\/annurev.biophys.27.1.249","article-title":"Inhibitors of HIV-1 protease: A major success of structure-assisted drug design.","volume":"27","author":"A Wlodawer","year":"1998","journal-title":"Annu Rev Biophys Biomol Struct"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.2174\/0929867023368890","article-title":"HIV protease inhibitors: Peptidomimetic drugs and future perspectives.","volume":"9","author":"HM Abdel-Rahman","year":"2002","journal-title":"Curr Med Chem"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.2174\/1568026043388312","article-title":"Non-peptidic HIV protease inhibitors.","volume":"4","author":"RA Chrusciel","year":"2004","journal-title":"Curr Top Med Chem"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.pbiomolbio.2004.07.001","article-title":"Crystallography and the design of anti-AIDS drugs: Conformational flexibility and positional adaptability are important in the design of non-nucleoside HIV-1 reverse transcriptase inhibitors.","volume":"88","author":"K Das","year":"2005","journal-title":"Prog Biophys Mol Biol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1126\/science.1377403","article-title":"Crystal structure at 3.5 \u00c5 resolution of HIV-1 reverse transcriptase complexed with an inhibitor.","volume":"256","author":"LA Kohlstaedt","year":"1992","journal-title":"Science"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"3911","DOI":"10.1073\/pnas.91.9.3911","article-title":"Structure of the binding site for nonnucleoside inhibitors of the reverse transcriptase of human immunodeficiency virus type 1.","volume":"91","author":"SJ Smerdon","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"3482","DOI":"10.1021\/jm0002679","article-title":"BCX-1812 (RWJ-270201): Discovery of a novel, highly potent, orally active, and selective influenza neuraminidase inhibitor through structure-based drug design.","volume":"43","author":"YS Babu","year":"2000","journal-title":"J Med Chem"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1006\/jmbi.1993.1461","article-title":"Three-dimensional structure of influenza A N9 neuraminidase and its complex with the inhibitor 2-deoxy 2,3-dehydro-N-acetyl neuraminic acid.","volume":"232","author":"P Bossart-Whitaker","year":"1993","journal-title":"J Mol Biol"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1021\/ja963036t","article-title":"Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: Design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity.","volume":"119","author":"CU Kim","year":"1997","journal-title":"J Am Chem Soc"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/363418a0","article-title":"Rational design of potent sialidase-based inhibitors of influenza virus replication.","volume":"363","author":"M von Itzstein","year":"1993","journal-title":"Nature"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0969-2126(97)00199-8","article-title":"The refined structure of human rhinovirus 16 at 2.15 \u00c5 resolution: Implications for the viral life cycle.","volume":"5","author":"AT Hadfield","year":"1997","journal-title":"Structure"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"8818","DOI":"10.1021\/ja0202560","article-title":"Characterization and crystal structure of a high-affinity pentavalent receptor-binding inhibitor for cholera toxin and <italic>E. coli<\/italic> heat-labile enterotoxin.","volume":"124","author":"EA Merritt","year":"2002","journal-title":"J Am Chem Soc"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"4941","DOI":"10.1021\/jm049592c","article-title":"Macrocyclic inhibitors for peptide deformylase: A structure-activity relationship study of the ring size.","volume":"47","author":"X Hu","year":"2004","journal-title":"J Med Chem"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"4790","DOI":"10.1021\/jm9802620","article-title":"Selective tight binding inhibitors of trypanosomal glyceraldehyde-3-phosphate dehydrogenase via structure-based drug design.","volume":"41","author":"AM Aronov","year":"1998","journal-title":"J Med Chem"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"4135","DOI":"10.1021\/jm000287a","article-title":"Adenosine analogues as inhibitors of <italic>Trypanosoma brucei<\/italic> phosphoglycerate kinase: Elucidation of a novel binding mode for a 2-amino-N(6)-substituted adenosine.","volume":"43","author":"JC Bressi","year":"2000","journal-title":"J Med Chem"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"13522","DOI":"10.1073\/pnas.212504399","article-title":"Crystal structure of human calcineurin complexed with cyclosporin A and human cyclophilin.","volume":"99","author":"L Jin","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S1074-5521(00)00134-4","article-title":"Structure-based drug design: The discovery of novel nonpeptide orally active inhibitors of human renin.","volume":"7","author":"J Rahuel","year":"2000","journal-title":"Chem Biol"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"4405","DOI":"10.1021\/jm020578e","article-title":"Structure-based design of novel guanidine\/benzamidine mimics: Potent and orally bioavailable factor Xa inhibitors as novel anticoagulants.","volume":"46","author":"PY Lam","year":"2003","journal-title":"J Med Chem"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"3730","DOI":"10.1021\/jm0306374","article-title":"Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors.","volume":"47","author":"T Terasaka","year":"2004","journal-title":"J Med Chem"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1126\/science.1095920","article-title":"Protein kinase inhibitors: Insights into drug design from structure.","volume":"303","author":"ME Noble","year":"2004","journal-title":"Science"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000530","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T18:35:52Z","timestamp":1539974152000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000530"}},"subtitle":[],"editor":[{"given":"Ernest","family":"Fraenkel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2009,10,26]]},"references-count":69,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2009,10,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1000530","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,10,26]]}}}