{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:57:52Z","timestamp":1785229072086,"version":"3.55.0"},"reference-count":83,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemPhysChem"],"published-print":{"date-parts":[[2023,5,16]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We present in this article a case study on the thermodynamics of binding to human carbonic anhydrase II (HCA II) by three well\u2010known inhibitors, <jats:italic>viz<\/jats:italic>. (a) acetazolamide (AZM) that directly binds to the catalytic Zn(II) ion at the active site, (b) non\u2010zinc binding 6\u2010hydroxy\u20102\u2010thioxocoumarin (FC5) (c) 2\u2010[(S)\u2010benzylsulfinyl]benzoic acid (3G1). In each case, the crystal structure or its analogue of inhibitor\u2010bound HCA II has been used to perform classical molecular dynamics (MD) simulation in water till <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/cphc202200770-math-0001.png\" xlink:title=\"urn:x-wiley:14394235:media:cphc202200770:cphc202200770-math-0001\"\/>\n. AZM and FC5 are found to undergo repeated binding and unbinding with markedly different dynamics from the partially buried, substrate\u2010binding hydrophobic pocket near the active site. 3G1, on the other hand, is found to remain mostly at its crystallographic binding site occluded from the active site of HCA II. The associated binding free energies (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/cphc202200770-math-0002.png\" xlink:title=\"urn:x-wiley:14394235:media:cphc202200770:cphc202200770-math-0002\"\/>\n) have been computed using the known MM\/GBSA method and compared to the available experimental data. Our results show that <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/cphc202200770-math-0003.png\" xlink:title=\"urn:x-wiley:14394235:media:cphc202200770:cphc202200770-math-0003\"\/>\n encounters several issues including limited sampling of multiple binding sites and incorrect prediction of the affinity of the chosen ligands. Possible use of the simulation results in further construction of Markov state models is also discussed.<\/jats:p>","DOI":"10.1002\/cphc.202200770","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T04:11:23Z","timestamp":1674619883000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Case Study on the Use of Binding Free Energies to Screen Inhibitors of Human Carbonic Anhydrase II"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2734-3965","authenticated-orcid":false,"given":"Satyajit","family":"Khatua","sequence":"first","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Kharagpur  Kharagpur 721302"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanusri","family":"De Bhowmik","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Kharagpur  Kharagpur 721302"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3330-6033","authenticated-orcid":false,"given":"Srabani","family":"Taraphder","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Kharagpur  Kharagpur 721302"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(03)00610-7"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096361"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr800551w"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11224-022-01955-7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","unstructured":"F. 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