{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:41:52Z","timestamp":1792028512903,"version":"4.4.0"},"reference-count":34,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Molecular Biology"],"published-print":{"date-parts":[[2010,4]]},"DOI":"10.1016\/j.jmb.2010.02.007","type":"journal-article","created":{"date-parts":[[2010,2,13]],"date-time":"2010-02-13T04:24:22Z","timestamp":1266035062000},"page":"1042-1054","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":150,"title":["Non-additivity of Functional Group Contributions in Protein\u2013Ligand Binding: A Comprehensive Study by Crystallography and Isothermal Titration Calorimetry"],"prefix":"10.1016","volume":"397","author":[{"given":"Bernhard","family":"Baum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laveena","family":"Muley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Smolinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Heine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hangauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Klebe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jmb.2010.02.007_bib1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1017\/S0033583506004240","article-title":"Designing ligands to bind proteins","volume":"38","author":"Whitesides","year":"2005","journal-title":"Q. Rev. Biophys."},{"key":"10.1016\/j.jmb.2010.02.007_bib2","doi-asserted-by":"crossref","first-page":"5912","DOI":"10.1021\/jm050362n","article-title":"A critical assessment of docking programs and scoring functions","volume":"49","author":"Warren","year":"2006","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.jmb.2010.02.007_bib3","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1023\/A:1008708418253","article-title":"Generating consistent sets of thermodynamic and structural data for analysis of protein-ligand interactions","volume":"20","author":"Davies","year":"2000","journal-title":"Persp. Drug Discov. Des."},{"key":"10.1016\/j.jmb.2010.02.007_bib4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nrd3054","article-title":"Adding calorimetric data to decision making in lead discovery: a hot tip","volume":"9","author":"Ladbury","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.jmb.2010.02.007_bib5","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.jmb.2006.07.067","article-title":"Thermodynamic penalty arising from burial of a ligand polar group within a hydrophobic pocket of a protein receptor","volume":"362","author":"Barratt","year":"2006","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2010.02.007_bib6","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1146\/annurev.biophys.34.040204.144517","article-title":"Modeling water, the hydrophobic effect, and ion solvation","volume":"34","author":"Dill","year":"2005","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"10.1016\/j.jmb.2010.02.007_bib7","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0959-440X(97)80028-0","article-title":"Entropy in protein folding and in protein-protein interactions","volume":"7","author":"Brady","year":"1997","journal-title":"Curr. Opin. Struct. Biol."},{"key":"10.1016\/j.jmb.2010.02.007_bib8","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1006\/jmbi.1994.1430","article-title":"Decomposition of the free energy of a system in terms of specific interactions. Implications for theoretical and experimental studies","volume":"240","author":"Mark","year":"1994","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2010.02.007_bib9","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1073\/pnas.90.4.1172","article-title":"Toward an estimation of binding constants in aqueous solution: studies of associations of vancomycin group antibiotics","volume":"90","author":"Williams","year":"1993","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10.1016\/j.jmb.2010.02.007_bib10","doi-asserted-by":"crossref","first-page":"6596","DOI":"10.1002\/anie.200300644","article-title":"Understanding noncovalent interactions: ligand binding energy and catalytic efficiency from ligand-induced reductions in motion within receptors and enzymes","volume":"43","author":"Williams","year":"2004","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"10.1016\/j.jmb.2010.02.007_bib11","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S0022-2836(03)00428-5","article-title":"Ligand binding energy and catalytic efficiency from improved packing within receptors and enzymes","volume":"329","author":"Williams","year":"2003","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2010.02.007_bib12","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.jmb.2005.11.015","article-title":"Ligand binding energy and enzyme efficiency from reductions in protein dynamics","volume":"355","author":"Williams","year":"2006","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2010.02.007_bib13","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S0022-2836(65)80285-6","article-title":"On the nature of allosteric transitions: a plausible model","volume":"12","author":"Monod","year":"1965","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2010.02.007_bib14","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.jmb.2009.06.016","article-title":"Think twice: understanding the high potency of bis(phenyl)methane inhibitors of thrombin","volume":"391","author":"Baum","year":"2009","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2010.02.007_bib15","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jmb.2009.04.051","article-title":"More than a simple lipophilic contact: a detailed thermodynamic analysis of nonbasic residues in the S1 pocket of thrombin","volume":"390","author":"Baum","year":"2009","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2010.02.007_bib16","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1432-1033.1992.tb16916.x","article-title":"The interaction of thrombin with fibrinogen. A structural basis for its specificity","volume":"206","author":"Stubbs","year":"1992","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.jmb.2010.02.007_bib17","doi-asserted-by":"crossref","unstructured":"Muley, L., Baum, B., Smolinski, M., Freindorf, M., Heine, A., Klebe, G. & Hangauer, D. (2010). Enhancement of hydrophobic interactions and hydrogen bond strength by cooperativity: Synthesis, modelling and molecular dynamics simulations of a congeneric series of thrombin inhibitors. J. Med. Chem. In the press. doi:10.1021\/jm9016416.","DOI":"10.1021\/jm9016416"},{"key":"10.1016\/j.jmb.2010.02.007_bib18","unstructured":"LSBU. http:\/\/www.lsbu.ac.uk\/biology\/enztech\/ph.html."},{"key":"10.1016\/j.jmb.2010.02.007_bib19","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.jmb.2007.08.063","article-title":"Tracing changes in protonation: a prerequisite to factorize thermodynamic data of inhibitor binding to aldose reductase","volume":"373","author":"Steuber","year":"2007","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2010.02.007_bib20","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/1074-5521(95)90097-7","article-title":"Win some, lose some: Enthalpy-entropy compensation in weak intermolecular interactions","volume":"2","author":"Dunitz","year":"1995","journal-title":"Chem. Biol."},{"key":"10.1016\/j.jmb.2010.02.007_bib21","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.jmb.2005.11.015","article-title":"Ligand binding energy and enzyme efficiency from reductions in protein dynamics","volume":"355","author":"Williams","year":"2006","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2010.02.007_bib22","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1126\/science.264.5159.670","article-title":"The entropic cost of bound water in crystals and biomolecules","volume":"264","author":"Dunitz","year":"1994","journal-title":"Science"},{"key":"10.1016\/j.jmb.2010.02.007_bib23","doi-asserted-by":"crossref","first-page":"8511","DOI":"10.1002\/anie.200701169","article-title":"Thermodynamic inhibition profile of a cyclopentyl and a cyclohexyl derivative towards thrombin: the same but for different reasons","volume":"46","author":"Gerlach","year":"2007","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"10.1016\/j.jmb.2010.02.007_bib24","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.jmb.2008.09.073","article-title":"The thermodynamics of protein\u2013ligand interaction and solvation: Insights for ligand design","volume":"384","author":"Olsson","year":"2008","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2010.02.007_bib25","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0049-3848(89)90232-6","article-title":"Synthetic inhibitors of bovine factor Xa and thrombin comparison of their anticoagulant efficiency","volume":"54","author":"Sturzebecher","year":"1989","journal-title":"Thromb. Res."},{"key":"10.1016\/j.jmb.2010.02.007_bib26","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1042\/bj1290197","article-title":"The graphical determination of Km and Ki","volume":"129","author":"Dixon","year":"1972","journal-title":"Biochem. J."},{"key":"10.1016\/j.jmb.2010.02.007_bib27","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0003-2697(89)90213-3","article-title":"Rapid measurement of binding constants and heats of binding using a new titration calorimeter","volume":"179","author":"Wiseman","year":"1989","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.jmb.2010.02.007_bib28","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","article-title":"Processing of X-ray diffraction data collected in oscillation mode","volume":"276","author":"Otwinowski","year":"1997","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.jmb.2010.02.007_bib29","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1006\/jmbi.2001.4872","article-title":"Inhibition of human alpha-thrombin by a phosphonate tripeptide proceeds via a metastable pentacoordinated phosphorus intermediate","volume":"311","author":"Skordalakes","year":"2001","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jmb.2010.02.007_bib30","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1107\/S0907444998003254","article-title":"Crystallography & NMR system: a new software suite for macromolecular structure determination","volume":"54","author":"Brunger","year":"1998","journal-title":"Acta Crystallogr. D"},{"key":"10.1016\/j.jmb.2010.02.007_bib31","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0076-6879(97)77018-6","article-title":"SHELXL: high-resolution refinement","volume":"277B","author":"Sheldrick","year":"1997","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.jmb.2010.02.007_bib32","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: model-building tools for molecular graphics","volume":"60","author":"Emsley","year":"2004","journal-title":"Acta Crystallogr. D"},{"key":"10.1016\/j.jmb.2010.02.007_bib33","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: a program to check the stereochemical quality of protein structures","volume":"26","author":"Laskowski","year":"1993","journal-title":"J. Appl. Crystallogr."},{"key":"10.1016\/j.jmb.2010.02.007_bib34","unstructured":"Kleywegt, G. J., Zou, J. Y., Kjeldgaard, M. & Jones, T. A. (2001). Around O. In International Tables for Crystallography (Rossmann, M. G. & Arnold, E., eds), vol. F, pp. 353\u2013356, 366\u2013367. Kluwer Academic Publishers, Dordrecht."}],"container-title":["Journal of Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022283610001622?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022283610001622?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T21:10:36Z","timestamp":1758316236000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022283610001622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2010,4]]}},"alternative-id":["S0022283610001622"],"URL":"https:\/\/doi.org\/10.1016\/j.jmb.2010.02.007","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.3205959.2891060","asserted-by":"object"}]},"ISSN":["0022-2836"],"issn-type":[{"value":"0022-2836","type":"print"}],"subject":[],"published":{"date-parts":[[2010,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Non-additivity of Functional Group Contributions in Protein\u2013Ligand Binding: A Comprehensive Study by Crystallography and Isothermal Titration Calorimetry","name":"articletitle","label":"Article Title"},{"value":"Journal of Molecular Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jmb.2010.02.007","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2010 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}