{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T16:13:26Z","timestamp":1772208806162,"version":"3.50.1"},"reference-count":74,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2009,10,9]],"date-time":"2009-10-09T00:00:00Z","timestamp":1255046400000},"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.1000528","type":"journal-article","created":{"date-parts":[[2009,10,8]],"date-time":"2009-10-08T17:53:37Z","timestamp":1255024417000},"page":"e1000528","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":151,"title":["High-Performance Drug Discovery: Computational Screening by Combining Docking and Molecular Dynamics Simulations"],"prefix":"10.1371","volume":"5","author":[{"given":"Noriaki","family":"Okimoto","sequence":"first","affiliation":[]},{"given":"Noriyuki","family":"Futatsugi","sequence":"additional","affiliation":[]},{"given":"Hideyoshi","family":"Fuji","sequence":"additional","affiliation":[]},{"given":"Atsushi","family":"Suenaga","sequence":"additional","affiliation":[]},{"given":"Gentaro","family":"Morimoto","sequence":"additional","affiliation":[]},{"given":"Ryoko","family":"Yanai","sequence":"additional","affiliation":[]},{"given":"Yousuke","family":"Ohno","sequence":"additional","affiliation":[]},{"given":"Tetsu","family":"Narumi","sequence":"additional","affiliation":[]},{"given":"Makoto","family":"Taiji","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2009,10,9]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/nbt1098-946","article-title":"Identification of a calcium channel modulator using a high throughput yeast two-hybrid screen.","volume":"16","author":"K Young","year":"1998","journal-title":"Nat Biotechnol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1006\/abio.1998.2740","article-title":"A high-throughput fluorescence screen to monitor the specific binding of antagonists to RNA targets.","volume":"261","author":"K Hamasaki","year":"1998","journal-title":"Anal Biochem"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1177\/108705719900400408","article-title":"A Homogenous 384-Well High Throughput Screen for Novel Tumor Necrosis Factor Receptor: Ligand Interactions Using Time Resolved Energy Transfer.","volume":"4","author":"KJ Moore","year":"1999","journal-title":"J Biomol Screen"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1177\/108705710000500310","article-title":"Ultra-high throughput screen of two-million-member combinatorial compound collection in a miniaturized, 1536-well assay format.","volume":"5","author":"D Dunn","year":"2000","journal-title":"J Biomol Screen"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1021\/jm010548w","article-title":"Molecular docking and high-throughput screening for novel inhibitors of protein tyrosine phosphatase-1B.","volume":"45","author":"TN Doman","year":"2002","journal-title":"J Med Chem"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1021\/cb700025j","article-title":"A fragment-based approach for the discovery of isoform-specific p38alpha inhibitors.","volume":"2","author":"J Chen","year":"2007","journal-title":"ACS Chem Biol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S1359-6446(05)03511-7","article-title":"Fragment-based lead discovery: leads by design.","volume":"10","author":"RA Carr","year":"2005","journal-title":"Drug Discov Today"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1021\/ci000403i","article-title":"Molecular complexity and its impact on the probability of finding leads for drug discovery.","volume":"41","author":"MM Hann","year":"2001","journal-title":"J Chem Inf Comput Sci"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0022-2836(95)80037-9","article-title":"Molecular recognition of receptor sites using a genetic algorithm with a description of desolvation.","volume":"245","author":"G Jones","year":"1995","journal-title":"J Mol Biol"},{"key":"ref10","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":"ref11","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":"ref12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1099-1352(199601)9:1<1::AID-JMR241>3.0.CO;2-6","article-title":"Automated docking of flexible ligands: applications of AutoDock.","volume":"9","author":"DS Goodsell","year":"1996","journal-title":"J Mol Recognit"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1021\/jm030644s","article-title":"Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening.","volume":"47","author":"TA Halgren","year":"2004","journal-title":"J Med Chem"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy.","volume":"47","author":"RA Friesner","year":"2004","journal-title":"J Med Chem"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1006\/jmbi.1996.0477","article-title":"A fast flexible docking method using an incremental construction algorithm.","volume":"261","author":"M Rarey","year":"1996","journal-title":"J Mol Biol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1023\/B:JCAM.0000017496.76572.6f","article-title":"Comparative study of several algorithms for flexible ligand docking.","volume":"17","author":"BD Bursulaya","year":"2003","journal-title":"J Comput Aided Mol Des"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1021\/jm0003992","article-title":"Detailed analysis of scoring functions for virtual screening.","volume":"44","author":"M Stahl","year":"2001","journal-title":"J Med Chem"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1021\/jm020495y","article-title":"Novel dihydrofolate reductase inhibitors. Structure-based versus diversity-based library design and high-throughput synthesis and screening.","volume":"46","author":"PC Wyss","year":"2003","journal-title":"J Med Chem"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1021\/jm0100279","article-title":"Are free energy calculations useful in practice? A comparison with rapid scoring functions for the p38 MAP kinase protein system.","volume":"44","author":"DA Pearlman","year":"2001","journal-title":"J Med Chem"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1021\/cr00023a004","article-title":"Free-Energy Calculations - Applications to Chemical and Biochemical Phenomena.","volume":"93","author":"P Kollman","year":"1993","journal-title":"Chemical Reviews"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1021\/ar010014p","article-title":"Ligand binding affinities from MD simulations.","volume":"35","author":"J Aqvist","year":"2002","journal-title":"Acc Chem Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1021\/ar000033j","article-title":"Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models.","volume":"33","author":"PA Kollman","year":"2000","journal-title":"Accounts of Chemical Research"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1021\/jm010338j","article-title":"Molecular dynamics and free energy analyses of cathepsin D-inhibitor interactions: insight into structure-based ligand design.","volume":"45","author":"S Huo","year":"2002","journal-title":"J Med Chem"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"5628","DOI":"10.1021\/jm030060q","article-title":"Investigation of neuraminidase-substrate recognition using molecular dynamics and free energy calculations.","volume":"46","author":"KM Masukawa","year":"2003","journal-title":"J Med Chem"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"4040","DOI":"10.1021\/jm049081q","article-title":"Validation and use of the MM-PBSA approach for drug discovery.","volume":"48","author":"B Kuhn","year":"2005","journal-title":"J Med Chem"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1021\/ci050289+","article-title":"New scoring functions for virtual screening from molecular dynamics simulations with a quantum-refined force-field (QRFF-MD). Application to cyclin-dependent kinase 2.","volume":"46","author":"P Ferrara","year":"2006","journal-title":"J Chem Inf Model"},{"key":"ref27","article-title":"A 185 Tflops simulation of amyloid-forming peptides from Yeast Prion Sup35 with the special-purpose computer System MD-GRAPE3.","author":"T Narumi","year":"2006"},{"key":"ref28","article-title":"MDGRAPE-3 chip: a 165 Gflops application specific LSI for molecular dynamics simulations.; 2004.","author":"M Taiji","year":"2004"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1021\/jm050554i","article-title":"Protein structures in virtual screening: A case study with CDK2.","volume":"49","author":"MP Thomas","year":"2006","journal-title":"J Med Chem"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1021\/jm0302997","article-title":"Evaluation of docking performance: comparative data on docking algorithms.","volume":"47","author":"M Kontoyianni","year":"2004","journal-title":"J Med Chem"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1021\/jm0203783","article-title":"Comparative evaluation of 11 scoring functions for molecular docking.","volume":"46","author":"R Wang","year":"2003","journal-title":"J Med Chem"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/jcc.20118","article-title":"The MPSim-Dock hierarchical docking algorithm: application to the eight trypsin inhibitor cocrystals.","volume":"26","author":"AE Cho","year":"2005","journal-title":"J Comput Chem"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1021\/jm030209y","article-title":"Lessons in molecular recognition: the effects of ligand and protein flexibility on molecular docking accuracy.","volume":"47","author":"JA Erickson","year":"2004","journal-title":"J Med Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"8260","DOI":"10.1021\/ja020429l","article-title":"Studying enzyme binding specificity in acetylcholinesterase using a combined molecular dynamics and multiple docking approach.","volume":"124","author":"J Kua","year":"2002","journal-title":"J Am Chem Soc"},{"key":"ref35","article-title":"Data mining: practical machine learning tools and techniques with java implementations","author":"IH Witten","year":"1999"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S0006-291X(03)00375-9","article-title":"Crystal structure of a histidine-tagged serine hydrolase involved in the carbazole degradation (CarC enzyme).","volume":"303","author":"H Habe","year":"2003","journal-title":"Biochem Biophys Res Commun"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1097\/00004424-199209000-00015","article-title":"Receiver operating characteristic rating analysis. Generalization to the population of readers and patients with the jackknife method.","volume":"27","author":"DD Dorfman","year":"1992","journal-title":"Invest Radiol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1016\/j.acra.2005.07.012","article-title":"Monte Carlo validation of the Dorfman-Berbaum-Metz method using normalized pseudovalues and less data-based model simplification.","volume":"12","author":"SL Hillis","year":"2005","journal-title":"Acad Radiol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1002\/sim.2024","article-title":"A comparison of the Dorfman-Berbaum-Metz and Obuchowski-Rockette methods for receiver operating characteristic (ROC) data.","volume":"24","author":"SL Hillis","year":"2005","journal-title":"Stat Med"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S1076-6332(97)80210-3","article-title":"Variance-component modeling in the analysis of receiver operating characteristic index estimates.","volume":"4","author":"CA Roe","year":"1997","journal-title":"Acad Radiol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/S1076-6332(97)80032-3","article-title":"Dorfman-Berbaum-Metz method for statistical analysis of multireader, multimodality receiver operating characteristic data: validation with computer simulation.","volume":"4","author":"CA Roe","year":"1997","journal-title":"Acad Radiol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/jcc.10379","article-title":"Converging free energy estimates: MM-PB(GB)SA studies on the protein-protein complex Ras-Raf.","volume":"25","author":"H Gohlke","year":"2004","journal-title":"Journal of Computational Chemistry"},{"key":"ref43","first-page":"192","article-title":"Conformational entropy of biomolecules: beyond the quasi-harmonic approximation.","volume":"18","author":"J Numata","year":"2007","journal-title":"Genome Inform"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1021\/ct0500904","article-title":"Evaluating the accuracy of the quasiharmonic approximation.","volume":"1","author":"CE Chang","year":"2005","journal-title":"Journal of Chemical Theory and Computation"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/nsb842","article-title":"Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor.","volume":"9","author":"TG Davies","year":"2002","journal-title":"Nat Struct Biol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1126\/science.291.5501.134","article-title":"Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors.","volume":"291","author":"ST Davis","year":"2001","journal-title":"Science"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S1367-5931(97)80038-5","article-title":"Computational approaches to molecular recognition.","volume":"1","author":"ML Lamb","year":"1997","journal-title":"Curr Opin Chem Biol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/prot.20223","article-title":"Relative free energy of binding and binding mode calculations of HIV-1 RT inhibitors based on dock-MM-PB\/GS.","volume":"57","author":"Z Zhou","year":"2004","journal-title":"Proteins"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"6789","DOI":"10.1021\/jm0608356","article-title":"Benchmarking sets for molecular docking.","volume":"49","author":"N Huang","year":"2006","journal-title":"J Med Chem"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1021\/ar000033j","article-title":"Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models.","volume":"33","author":"PA Kollman","year":"2000","journal-title":"Acc Chem Res"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S1074-5521(00)00104-6","article-title":"Structural basis for selectivity of a small molecule, S1-binding, submicromolar inhibitor of urokinase-type plasminogen activator.","volume":"7","author":"BA Katz","year":"2000","journal-title":"Chem Biol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"12325","DOI":"10.1074\/jbc.273.20.12325","article-title":"Molecular recognition of cyclic urea HIV-1 protease inhibitors.","volume":"273","author":"PJ Ala","year":"1998","journal-title":"J Biol Chem"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"2970","DOI":"10.1021\/bi011652i","article-title":"3D structure of Torpedo californica acetylcholinesterase complexed with huprine X at 2.1 A resolution: kinetic and molecular dynamic correlates.","volume":"41","author":"H Dvir","year":"2002","journal-title":"Biochemistry"},{"key":"ref54"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings.","volume":"46","author":"CA Lipinski","year":"2001","journal-title":"Adv Drug Deliv Rev"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"4111","DOI":"10.1021\/jm048957q","article-title":"The PDBbind database: methodologies and updates.","volume":"48","author":"R Wang","year":"2005","journal-title":"J Med Chem"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1021\/jm030580l","article-title":"The PDBbind database: collection of binding affinities for protein-ligand complexes with known three-dimensional structures.","volume":"47","author":"R Wang","year":"2004","journal-title":"J Med Chem"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1126\/science.281.5376.533","article-title":"Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors.","volume":"281","author":"NS Gray","year":"1998","journal-title":"Science"},{"key":"ref59"},{"key":"ref60","first-page":"1","article-title":"A method of establishing groups of equal amplitude in a plant based on similarity of species content and its applications to analysis of vegetation on Danish commons.","volume":"5","author":"T S\u00f8renson","year":"1948","journal-title":"Biologiske Skrifter"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"4422","DOI":"10.1021\/jm991090p","article-title":"Two-stage method for protein-ligand docking.","volume":"42","author":"D Hoffmann","year":"1999","journal-title":"J Med Chem"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of Simple Potential Functions for Simulating Liquid Water.","volume":"79","author":"WL Jorgensen","year":"1983","journal-title":"Journal of Chemical Physics"},{"key":"ref63","article-title":"AMBER 8","author":"DA Case","year":"2004"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1002\/jcc.10349","article-title":"A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations.","volume":"24","author":"Y Duan","year":"2003","journal-title":"J Comput Chem"},{"key":"ref65","first-page":"3684","article-title":"Molecular dynamics with coupling to an external bath.","volume":"81","author":"HJC Berendsen","year":"1984","journal-title":"J Comput Phys"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development and testing of a general amber force field.","volume":"25","author":"J Wang","year":"2004","journal-title":"J Comput Chem"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1002\/jcc.10128","article-title":"Fast, efficient generation of high-quality atomic charges. AM1-BCC model: II. Parameterization and validation.","volume":"23","author":"A Jakalian","year":"2002","journal-title":"J Comput Chem"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/(SICI)1096-987X(20000130)21:2<132::AID-JCC5>3.0.CO;2-P","article-title":"Fast, efficient generation of high-quality atomic Charges. AM1-BCC model: I. Method.","volume":"21","author":"A Jakalian","year":"2000","journal-title":"Journal of Computational Chemistry"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"6507","DOI":"10.1021\/jp010454y","article-title":"Extending the applicability of the nonlinear poisson-boltzmann equation: multiple dielectric constants and multivalent ions.","volume":"105","author":"W Rocchia","year":"2001","journal-title":"J Phys Chem B"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/jcc.1161","article-title":"Rapid grid-based construction of the molecular surface and the use of induced surface charge to calculate reaction field energies: applications to the molecular systems and geometric objects.","volume":"23","author":"W Rocchia","year":"2002","journal-title":"J Comput Chem"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1021\/j100058a043","article-title":"Accurate calculation of hydration free energies using macroscopic solvent models.","volume":"98","author":"D Sitkoff","year":"1994","journal-title":"J Phys Chem"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1021\/ct049834o","article-title":"Optimized radii for Poisson-Boltzmann calculations with the AMBER force field.","volume":"1","author":"JMJ Swanson","year":"2005","journal-title":"Journal of Chemical Theory and Computation"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/(SICI)1097-0282(199603)38:3<305::AID-BIP4>3.0.CO;2-Y","article-title":"Reduced surface: an efficient way to compute molecular surfaces.","volume":"38","author":"MF Sanner","year":"1996","journal-title":"Biopolymers"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1021\/ma00137a013","article-title":"Evaluation of the Configurational Entropy for Proteins - Application to Molecular-Dynamics Simulations of an Alpha-Helix.","volume":"17","author":"RM Levy","year":"1984","journal-title":"Macromolecules"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000528","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T22:25:20Z","timestamp":1558563920000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000528"}},"subtitle":[],"editor":[{"given":"David","family":"Case","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2009,10,9]]},"references-count":74,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2009,10,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1000528","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,10,9]]}}}