{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:21:56Z","timestamp":1788492116915,"version":"build-2803163510"},"reference-count":99,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T00:00:00Z","timestamp":1667865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polish Ministry of Science and Higher Education","award":["8211104160\/K19W03D10"],"award-info":[{"award-number":["8211104160\/K19W03D10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>It is postulated that the overexpression of Carbonic Anhydrase isozyme IX in some cancers contributes to the acidification of the extracellular matrix. It was proved that this promotes the growth and metastasis of the tumor. These observations have made Carbonic Anhydrase IX an attractive drug target. In the light of the findings and importance of the glycoprotein in the cancer treatment, we have employed quantum\u2013chemical approaches to study non-covalent interactions in the binding pocket. As a ligand, the acetazolamide (AZM) molecule was chosen, being known as a potential inhibitor exhibiting anticancer properties. First-Principles Molecular Dynamics was performed to study the chalcogen and other non-covalent interactions in the AZM ligand and its complexes with amino acids forming the binding site. Based on Density Functional Theory (DFT) and post-Hartree\u2013Fock methods, the metric and electronic structure parameters were described. The Non-Covalent Interaction (NCI) index and Atoms in Molecules (AIM) methods were applied for qualitative\/quantitative analyses of the non-covalent interactions. Finally, the AZM\u2013binding pocket interaction energy decomposition was carried out. Chalcogen bonding in the AZM molecule is an important factor stabilizing the preferred conformation. Free energy mapping via metadynamics and Path Integral molecular dynamics confirmed the significance of the chalcogen bond in structuring the conformational flexibility of the systems. The developed models are useful in the design of new inhibitors with desired pharmacological properties.<\/jats:p>","DOI":"10.3390\/ijms232213701","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T08:52:56Z","timestamp":1667897576000},"page":"13701","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Chalcogen Bond as a Factor Stabilizing Ligand Conformation in the Binding Pocket of Carbonic Anhydrase IX Receptor Mimic"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9712-6862","authenticated-orcid":false,"given":"Kamil","family":"Wojtkowiak","sequence":"first","affiliation":[{"name":"Faculty of Chemistry, University of Wroc\u0142aw, ul. F. Joliot-Curie 14, 50-383 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6495-6963","authenticated-orcid":false,"given":"Mariusz","family":"Michalczyk","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Wroc\u0142aw University of Science and Technology, Wybrze\u017ce Wyspia\u0144skiego 27, 50-370 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4038-5959","authenticated-orcid":false,"given":"Wiktor","family":"Zierkiewicz","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Wroc\u0142aw University of Science and Technology, Wybrze\u017ce Wyspia\u0144skiego 27, 50-370 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6601-9124","authenticated-orcid":false,"given":"Aneta","family":"Jezierska","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Wroc\u0142aw, ul. F. Joliot-Curie 14, 50-383 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2952-9739","authenticated-orcid":false,"given":"Jaros\u0142aw J.","family":"Panek","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Wroc\u0142aw, ul. F. Joliot-Curie 14, 50-383 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,8]]},"reference":[{"key":"ref_1","first-page":"143","article-title":"Noncovalent Interactions: A Challenge for Experiment and Theory","volume":"100","author":"Hobza","year":"1999","journal-title":"Chem. Rev."},{"key":"ref_2","first-page":"20160001","article-title":"Noncovalent interactions in biocomplexes","volume":"1","author":"Yamauchi","year":"2016","journal-title":"Phys. Sci. Rev."},{"key":"ref_3","unstructured":"McNaught, A.D., and Wilkinson, A. (2014). Lewis acid. 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