{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T22:03:25Z","timestamp":1789855405428,"version":"4.0.1"},"reference-count":20,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,10,24]]},"abstract":"\n The idea that enzymes accelerate their reactions by entropic\n effects has played a major role in many prominent proposals about the\n origin of enzyme catalysis. This idea implies that the binding to an\n enzyme active site freezes the motion of the reacting fragments and\n eliminates their entropic contributions,\n (\u0394\n S<\/jats:italic>\n cat<\/jats:sub>\n \u2021<\/jats:sup>\n )\u2032, to the\n activation energy. It is also implied that the binding entropy is equal\n to the activation entropy,\n (\u0394\n S<\/jats:italic>\n w<\/jats:sub>\n \u2021<\/jats:sup>\n )\u2032, of the\n corresponding solution reaction. It is, however, difficult to examine\n this idea by experimental approaches. The present paper defines the\n entropic proposal in a rigorous way and develops a computer simulation\n approach that determines (\u0394\n S<\/jats:italic>\n \u2021<\/jats:sup>\n )\u2032. This\n approach allows us to evaluate the differences between\n (\u0394\n S<\/jats:italic>\n \u2021<\/jats:sup>\n )\u2032 of an enzymatic reaction and of the\n corresponding reference reaction in solution. Our approach is used in a\n study of the entropic contribution to the catalytic reaction of\n subtilisin. It is found that this contribution is much smaller than\n previously thought. This result is due to the following:\n (\n i<\/jats:italic>\n ) Many of the motions that are free in the\n reactants state of the reference solution reaction are also free at the\n transition state. (\n ii<\/jats:italic>\n ) The binding to the enzyme\n does not completely freeze the motion of the reacting fragments so that\n (\u0394\n S<\/jats:italic>\n \u2021<\/jats:sup>\n )\u2032 in the enzymes is not zero.\n (\n iii<\/jats:italic>\n ) The binding entropy is not necessarily equal\n to (\u0394\n S<\/jats:italic>\n w<\/jats:sub>\n \u2021<\/jats:sup>\n )\u2032.\n <\/jats:p>","DOI":"10.1073\/pnas.97.22.11899","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:45:09Z","timestamp":1027680309000},"page":"11899-11904","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":160,"title":["How important are entropic contributions to enzyme catalysis?"],"prefix":"10.1073","volume":"97","author":[{"given":"J.","family":"Vill\u00e0","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Southern California, Los\r Angeles, CA 90089"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"\u0160trajbl","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Southern California, Los\r Angeles, CA 90089"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. M.","family":"Glennon","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Southern California, Los\r Angeles, CA 90089"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. Y.","family":"Sham","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Southern California, Los\r Angeles, CA 90089"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z. T.","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Southern California, Los\r Angeles, CA 90089"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Warshel","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Southern California, Los\r Angeles, CA 90089"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,10,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.68.8.1678"},{"key":"e_1_3_3_2_2","volume-title":"Catalysis in Chemistry and Enzymology","author":"Jencks W P","year":"1986","unstructured":"W P Jencks Catalysis in Chemistry and Enzymology (Dover, New York, 1986)."},{"key":"e_1_3_3_3_2","volume-title":"Mechanism in Protein Chemistry","author":"Kyte J","year":"1995","unstructured":"J Kyte Mechanism in Protein Chemistry (Garland, Hamden, CT, 1995)."},{"key":"e_1_3_3_4_2","volume-title":"Fundamentals of Organic and Biological Chemistry","author":"McMurry J","year":"1999","unstructured":"J McMurry, M E Castellion Fundamentals of Organic and Biological Chemistry (Prentice\u2013Hall, Englewood Cliffs, NJ, 1999)."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(00)00125-8"},{"key":"e_1_3_3_6_2","volume-title":"Computer Modeling of Chemical Reactions in Enzymes and Solutions","author":"Warshel A","year":"1991","unstructured":"A Warshel Computer Modeling of Chemical Reactions in Enzymes and Solutions (Wiley, New York, 1991)."},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.42.27035"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi000914y"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar960131y"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physchem.49.1.531"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja963568"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja972723x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja992218v"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp0003095"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00296a024"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(88)90445-7"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540140205"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja992441s"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01057a026"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1874-6047(08)60183-3"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.97.22.11899","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T17:42:20Z","timestamp":1649871740000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.97.22.11899"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,10,24]]},"references-count":20,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2000,10,24]]}},"alternative-id":["10.1073\/pnas.97.22.11899"],"URL":"https:\/\/doi.org\/10.1073\/pnas.97.22.11899","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,10,24]]},"assertion":[{"value":"2000-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-08-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-10-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}