{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:09:39Z","timestamp":1773277779773,"version":"3.50.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"15","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1587,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: The laws of thermodynamics describe a direct, quantitative relationship between metabolite concentrations and reaction directionality. Despite great efforts, thermodynamic data suffer from limited coverage, scattered accessibility and non-standard annotations. We present a framework for unifying thermodynamic data from multiple sources and demonstrate two new techniques for extrapolating the Gibbs energies of unmeasured reactions and conditions.<\/jats:p><jats:p>Results: Both methods account for changes in cellular conditions (pH, ionic strength, etc.) by using linear regression over the \u0394G\u25cb of pseudoisomers and reactions. The Pseudoisomeric Reactant Contribution method systematically infers compound formation energies using measured K\u2032 and pKa data. The Pseudoisomeric Group Contribution method extends the group contribution method and achieves a high coverage of unmeasured reactions. We define a continuous index that predicts the reversibility of a reaction under a given physiological concentration range. In the characteristic physiological range 3\u03bcM\u20133mM, we find that roughly half of the reactions in Escherichia coli's metabolism are reversible. These new tools can increase the accuracy of thermodynamic-based models, especially in non-standard pH and ionic strengths. The reversibility index can help modelers decide which reactions are reversible in physiological conditions.<\/jats:p><jats:p>Availability: Freely available on the web at: http:\/\/equilibrator.weizmann.ac.il. Website implemented in Python, MySQL, Apache and Django, with all major browsers supported. The framework is open-source (code.google.com\/p\/milo-lab), implemented in pure Python and tested mainly on Linux.<\/jats:p><jats:p>Contact: \u00a0ron.milo@weizmann.ac.il<\/jats:p><jats:p>Supplementary Information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts317","type":"journal-article","created":{"date-parts":[[2012,5,30]],"date-time":"2012-05-30T02:10:12Z","timestamp":1338343812000},"page":"2037-2044","source":"Crossref","is-referenced-by-count":115,"title":["An integrated open framework for thermodynamics of reactions that combines accuracy and coverage"],"prefix":"10.1093","volume":"28","author":[{"given":"Elad","family":"Noor","sequence":"first","affiliation":[{"name":"1 Department of Plant Sciences and 2Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel"}]},{"given":"Arren","family":"Bar-Even","sequence":"additional","affiliation":[{"name":"1 Department of Plant Sciences and 2Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel"}]},{"given":"Avi","family":"Flamholz","sequence":"additional","affiliation":[{"name":"1 Department of Plant Sciences and 2Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel"}]},{"given":"Yaniv","family":"Lubling","sequence":"additional","affiliation":[{"name":"1 Department of Plant Sciences and 2Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel"}]},{"given":"Dan","family":"Davidi","sequence":"additional","affiliation":[{"name":"1 Department of Plant Sciences and 2Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel"}]},{"given":"Ron","family":"Milo","sequence":"additional","affiliation":[{"name":"1 Department of Plant Sciences and 2Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel"}]}],"member":"286","published-online":{"date-parts":[[2012,5,29]]},"reference":[{"key":"2023012512451848100_B1","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.1073\/pnas.88.8.3268","article-title":"Equilibrium compositions of solutions of biochemical species and heats of biochemical reactions Biochemistry: Alberty","volume":"88","author":"Alberty","year":"1991","journal-title":"Proc. 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