{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T13:55:05Z","timestamp":1765806905754},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2010,8,12]],"date-time":"2010-08-12T00:00:00Z","timestamp":1281571200000},"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.1000880","type":"journal-article","created":{"date-parts":[[2010,8,12]],"date-time":"2010-08-12T19:52:07Z","timestamp":1281642727000},"page":"e1000880","update-policy":"http:\/\/dx.doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Computational Analysis of Phosphopeptide Binding to the Polo-Box Domain of the Mitotic Kinase PLK1 Using Molecular Dynamics Simulation"],"prefix":"10.1371","volume":"6","author":[{"given":"David J.","family":"Huggins","sequence":"first","affiliation":[]},{"given":"Grahame J.","family":"McKenzie","sequence":"additional","affiliation":[]},{"given":"Daniel D.","family":"Robinson","sequence":"additional","affiliation":[]},{"given":"Ana J.","family":"Narv\u00e1ez","sequence":"additional","affiliation":[]},{"given":"Bryn","family":"Hardwick","sequence":"additional","affiliation":[]},{"given":"Meredith","family":"Roberts-Thomson","sequence":"additional","affiliation":[]},{"given":"Ashok R.","family":"Venkitaraman","sequence":"additional","affiliation":[]},{"given":"Guy H.","family":"Grant","sequence":"additional","affiliation":[]},{"given":"Mike C.","family":"Payne","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2010,8,12]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nrm1401","article-title":"Polo-like kinases and the orchestration of cell division.","volume":"5","author":"FA Barr","year":"2004","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/sj.onc.1208280","article-title":"Structure and function of Polo-like kinases.","volume":"24","author":"DM Lowery","year":"2005","journal-title":"Oncogene"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.devcel.2008.04.014","article-title":"Polo on the rise - from mitotic entry to cytokinesis with Plk1.","volume":"14","author":"M Petronczki","year":"2008","journal-title":"Dev Cell"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/sj.onc.1208218","article-title":"Regulation of cell cycle checkpoints by polo-like kinases.","volume":"24","author":"SQ Xie","year":"2005","journal-title":"Oncogene"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nrc1841","article-title":"Targeting polo-like kinase 1 for cancer therapy.","volume":"6","author":"K Strebhardt","year":"2006","journal-title":"Nat Rev Cancer"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"4419","DOI":"10.1073\/pnas.0307700101","article-title":"M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCF beta-TrCP.","volume":"101","author":"N Watanabe","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/35065617","article-title":"Polo-like kinase 1 phosphorylates cyclin B1 and targets it to the nucleus during prophase.","volume":"410","author":"F Toyoshima-Morimoto","year":"2001","journal-title":"Nature"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1126\/science.273.5280.1377","article-title":"Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts.","volume":"273","author":"A Kumagai","year":"1996","journal-title":"Science"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1126\/science.1079079","article-title":"Proteomic screen finds pSer\/pThr-binding domain localizing Plk1 to mitotic substrates.","volume":"299","author":"AEH Elia","year":"2003","journal-title":"Science"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0092-8674(03)00725-6","article-title":"The molecular basis for phosphodependent substrate targeting and regulation of Plks by the Polo-box domain.","volume":"115","author":"AEH Elia","year":"2003","journal-title":"Cell"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1038\/sj.emboj.7601683","article-title":"Proteomic screen defines the Polo-box domain interactome and identifies Rock2 as a Plk1 substrate.","volume":"26","author":"DM Lowery","year":"2007","journal-title":"Embo J"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"5757","DOI":"10.1093\/emboj\/cdg558","article-title":"The crystal structure of the human polo-like kinase-1 polo box domain and its phospho-peptide complex.","volume":"22","author":"KY Cheng","year":"2003","journal-title":"Embo J"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1073\/pnas.0609131104","article-title":"Molecular and structural basis of polo-like kinase 1 substrate recognition: Implications in centrosomal localization.","volume":"104","author":"B Garcia-Alvarez","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1038\/nsmb.1628","article-title":"Structural and functional analyses of minimal phosphopeptides targeting the polo-box domain of polo-like kinase 1.","volume":"16","author":"SM Yun","year":"2009","journal-title":"Nat Struct Mol Biol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1126\/science.1083653","article-title":"Assembly of cell regulatory systems through protein interaction domains.","volume":"300","author":"T Pawson","year":"2003","journal-title":"Science"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1091\/mbc.E05-08-0801","article-title":"Different Plk1 functions show distinct dependencies on Polo-Box domain-mediated targeting.","volume":"17","author":"A Hanisch","year":"2006","journal-title":"Mol Biol Cell"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"18891","DOI":"10.1074\/jbc.M500982200","article-title":"A structural basis for 14-3-3sigma functional specificity.","volume":"280","author":"EW Wilker","year":"2005","journal-title":"J Biol Chem"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.cell.2007.09.041","article-title":"RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly.","volume":"131","author":"MS Huen","year":"2007","journal-title":"Cell"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/S1097-2765(00)00114-3","article-title":"The molecular basis of FHA Domain : Phosphopeptide binding specificity and implications for phospho-dependent signaling mechanisms.","volume":"6","author":"D Durocher","year":"2000","journal-title":"Mol Cell"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/nsb0902-646","article-title":"Molecular dynamics simulations of biomolecules.","volume":"9","author":"M Karplus","year":"2002","journal-title":"Nat Struct Biol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1021\/jp807701h","article-title":"Computations of standard binding free energies with molecular dynamics simulations.","volume":"113","author":"Y Deng","year":"2009","journal-title":"J Phys Chem B"},{"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":"Acc Chem Res"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0006-3495(03)74462-2","article-title":"Protocol for MM\/PBSA molecular dynamics simulations of proteins.","volume":"85","author":"F Fogolari","year":"2003","journal-title":"Biophys J"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1021\/ct8003707","article-title":"MM-PBSA Captures Key Role of Intercalating Water Molecules at a Protein-Protein Interface.","volume":"5","author":"S Wong","year":"2009","journal-title":"J Chem Theory Comput"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1371\/journal.pcbi.0020001","article-title":"Computational analysis and prediction of the binding motif and protein interacting partners of the Abl SH3 domain.","volume":"2","author":"T Hou","year":"2006","journal-title":"PLoS Comput Biol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.theochem.2006.11.010","article-title":"Role of water molecules for binding inhibitors in the SH2 domain of Grb2: A molecular dynamics study.","volume":"806","author":"V Leroux","year":"2007","journal-title":"J Mol Struct -Theochem"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/jcc.540040211","article-title":"Charmm - a Program for Macromolecular Energy, Minimization, and Dynamics Calculations.","volume":"4","author":"BR Brooks","year":"1983","journal-title":"J Comput Chem"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1021\/jp973084f","article-title":"All-atom empirical potential for molecular modeling and dynamics studies of proteins.","volume":"102","author":"AD MacKerell","year":"1998","journal-title":"J Phys Chem B"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"7510","DOI":"10.1021\/jp0007843","article-title":"An improved empirical potential energy function for molecular simulations of phospholipids.","volume":"104","author":"SE Feller","year":"2000","journal-title":"J Phys Chem B"},{"key":"ref30","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":"J Chem Phys"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes.","volume":"23","author":"JP Ryckaert","year":"1977","journal-title":"J Comput Phys"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/0009-2614(84)80098-6","article-title":"Stochastic boundary conditions for molecular dynamics simulations of ST2 water.","volume":"105","author":"A Brunger","year":"1984","journal-title":"Chem Phys Lett"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"S199","DOI":"10.1098\/rsif.2008.0331.focus","article-title":"Dynamics of conserved waters in human Hsp90: implications for drug design.","volume":"5","author":"A Yan","year":"2008","journal-title":"J R Soc Interface"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/prot.340040104","article-title":"Calculation of the Total Electrostatic Energy of a Macromolecular System - Solvation Energies, Binding-Energies, and Conformational-Analysis.","volume":"4","author":"MK Gilson","year":"1988","journal-title":"Proteins-Structure Function and Genetics"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/jcc.540090407","article-title":"Calculating the Electrostatic Potential of Molecules in Solution - Method and Error Assessment.","volume":"9","author":"MK Gilson","year":"1988","journal-title":"J Comput Chem"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/jcc.540120405","article-title":"A rapid finite difference algorithm, utilizing successive over-relaxation to solve the Poisson-Boltzmann equation.","volume":"12","author":"A Nicholls","year":"1991","journal-title":"J Comput Chem"},{"key":"ref37","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":"ref38","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jmgm.2004.05.003","article-title":"Comparative estimation of vibrational entropy changes in proteins through normal modes analysis.","volume":"23","author":"BJ Carrington","year":"2004","journal-title":"J Mol Graph Model"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1039\/B612449F","article-title":"Water at biomolecular binding interfaces.","volume":"9","author":"Z Li","year":"2007","journal-title":"Phys Chem Chem Phys"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"13337","DOI":"10.1021\/jp9047456","article-title":"Prediction of the Water Content in Protein Binding Sites.","volume":"113","author":"J Michel","year":"2009","journal-title":"J Phys Chem B"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"7683","DOI":"10.1021\/ja0377908","article-title":"Standard free energy of releasing a localized water molecule from the binding pockets of proteins: double-decoupling method.","volume":"126","author":"D Hamelberg","year":"2004","journal-title":"J Am Chem Soc"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"4964","DOI":"10.1021\/jp994261a","article-title":"Solvent reorganization energy and entropy in hydrophobic hydration.","volume":"104","author":"T Lazaridis","year":"2000","journal-title":"J Phys Chem B"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1073\/pnas.0610202104","article-title":"Motifs for molecular recognition exploiting hydrophobic enclosure in protein-ligand binding.","volume":"104","author":"T Young","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1021\/ja0771033","article-title":"Role of the active-site solvent in the thermodynamics of factor Xa ligand binding.","volume":"130","author":"R Abel","year":"2008","journal-title":"J Am Chem Soc"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1002\/pro.177","article-title":"High-energy water sites determine peptide binding affinity and specificity of PDZ domains.","volume":"18","author":"T Beuming","year":"2009","journal-title":"Protein Sci"},{"key":"ref46","article-title":"D. E. Shaw Research NY, NY (USA)."},{"key":"ref47","doi-asserted-by":"crossref","first-page":"11225","DOI":"10.1021\/ja9621760","article-title":"Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids.","volume":"118","author":"WL Jorgensen","year":"1996","journal-title":"J Am Chem Soc"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1080\/00268978500103111","article-title":"Temperature and Size Dependence for Monte-Carlo Simulations of Tip4P Water.","volume":"56","author":"WL Jorgensen","year":"1985","journal-title":"Mol Phys"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1006\/abio.1997.2042","article-title":"A fluorescence polarization based Src-SH2 binding assay.","volume":"247","author":"BA Lynch","year":"1997","journal-title":"Anal Biochem"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/nsb1296-998","article-title":"The role of water in sequence-independent ligand binding by an oligopeptide transporter protein.","volume":"3","author":"JRH Tame","year":"1996","journal-title":"Nat Struct Biol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"5147","DOI":"10.1021\/bi982974y","article-title":"Calorimetric examination of high-affinity Src SH2 domain-tyrosyl phosphopeptide binding: Dissection of the phosphopeptide sequence specificity and coupling energetics.","volume":"38","author":"JM Bradshaw","year":"1999","journal-title":"Biochemistry"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/340404a0","article-title":"Substrate specificity and affinity of a protein modulated by bound water molecules.","volume":"340","author":"FA Quiocho","year":"1989","journal-title":"Nature"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S1074-5521(96)90164-7","article-title":"Just add water! The effect of water on the specificity of protein-ligand binding sites and its potential application to drug design.","volume":"3","author":"JE Ladbury","year":"1996","journal-title":"Chem Biol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1146\/annurev.biophys.35.040405.102134","article-title":"Water mediation in protein folding and molecular recognition.","volume":"35","author":"Y Levy","year":"2006","journal-title":"Annu Rev Biophys Biomol Struct"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1021\/cr068037a","article-title":"Water as an active constituent in cell biology.","volume":"108","author":"P Ball","year":"2008","journal-title":"Chem Rev"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1124\/jpet.102.036350","article-title":"The identification and characterization of the marine natural product scytonemin as a novel antiproliferative pharmacophore.","volume":"303","author":"CS Stevenson","year":"2002","journal-title":"J Pharmacol Exp Ther"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.chembiol.2004.11.009","article-title":"Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase.","volume":"12","author":"Y Liu","year":"2005","journal-title":"Chem Biol"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.ccr.2005.02.009","article-title":"ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent.","volume":"7","author":"K Gumireddy","year":"2005","journal-title":"Cancer Cell"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/nchembio825","article-title":"Inhibitors of Polo-like kinase reveal roles in spindle-pole maintenance.","volume":"2","author":"C McInnes","year":"2006","journal-title":"Nat Chem Biol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.cub.2006.12.037","article-title":"BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo.","volume":"17","author":"M Steegmaier","year":"2007","journal-title":"Curr Biol"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1158\/1535-7163.MCT-06-0543","article-title":"In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1.","volume":"6","author":"TJ Lansing","year":"2007","journal-title":"Mol Cancer Ther"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1128\/MCB.26.6.2093-2108.2006","article-title":"Normal cells, but not cancer cells, survive severe Plk1 depletion.","volume":"26","author":"X Liu","year":"2006","journal-title":"Mol Cell Biol"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"5789","DOI":"10.1073\/pnas.1031523100","article-title":"Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells.","volume":"100","author":"X Liu","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.chembiol.2008.03.013","article-title":"Inhibition of polo-like kinase 1 by blocking polo-box domain-dependent protein-protein interactions.","volume":"15","author":"W Reindl","year":"2008","journal-title":"Chem Biol"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1074\/jbc.M805308200","article-title":"Deficiency in chromosome congression by the inhibition of Plk1 polo box domain-dependent recognition.","volume":"284","author":"N Watanabe","year":"2009","journal-title":"J Biol Chem"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1021\/ml100020e","article-title":"Probing Binding Modes of Small Molecule Inhibitors to the Polo-Box Domain of Human Polo-like Kinase 1.","volume":"1","author":"C Liao","year":"2010","journal-title":"ACS Med Chem Lett"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000880","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T18:45:33Z","timestamp":1539974733000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000880"}},"subtitle":[],"editor":[{"given":"Kyung","family":"Lee","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2010,8,12]]},"references-count":66,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2010,8,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1000880","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,8,12]]}}}