{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:25:14Z","timestamp":1787034314441,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["11241091"],"award-info":[{"award-number":["11241091"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1251871"],"award-info":[{"award-number":["1251871"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["11220444"],"award-info":[{"award-number":["11220444"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Gingipain B is a protease released by\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    , which contributes to the development of diseases such as periodontitis, Alzheimer's disease, rheumatoid arthritis and cancer. Therefore, it could be a key target for the design of inhibitors that could be used in new drug therapies. In this search for inhibitors, it is interesting to study their potentiation by Zn\n                    <jats:sup>2+<\/jats:sup>\n                    , mainly because this divalent cation can be a common additive in toothpastes or mouthwashes. To understand this potentiation process, the structural aspects that determine the effect of Zn\n                    <jats:sup>2+<\/jats:sup>\n                    on the different potentiation of gingipain B inhibition by three inhibitors with benzamidine group were studied. For this purpose, molecular dynamics simulations of the enzyme\/inhibitor complex, in the presence or absence of Zn\n                    <jats:sup>2+<\/jats:sup>\n                    , were performed to identify the residues involved in the interaction with the inhibitor or with the cation. From the simulations it is observed that the compounds that are potentiated by Zn interact with the ion via water molecules, which are oriented towards the carbonyl functional group. In addition, a higher solvent exposure of the catalytic site and a lower flexibility of a region adjacent to cysteine 244, which participates in catalysis, are observed in the simulations. The structural and dynamic results obtained through molecular dynamics simulations support the hypothesis that the potentiation of gingipain B inhibition by Zn\n                    <jats:sup>2+<\/jats:sup>\n                    is associated with ion\u2010mediated ligand stabilization, leading to a decrease in the number of water molecules in the second hydration shell, as well as polarization of the molecules in the vicinity of Zn\n                    <jats:sup>2+<\/jats:sup>\n                    . Taken together, these findings open new avenues for the design of inhibitors whose activity can be modulated or enhanced by the presence of Zn\n                    <jats:sup>2+<\/jats:sup>\n                    , with potential applications in the development of innovative therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1002\/prot.70167","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:36:41Z","timestamp":1787031401000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural Determinants of Zn\n                    <sup>2+<\/sup>\n                    Potentiation of Gingipain B Inhibition of\n                    <scp>\n                      <i>Porphyromonas gingivalis<\/i>\n                    <\/scp>\n                    by Compounds With the Benzamidine Group: A Computational Study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8993-9353","authenticated-orcid":false,"given":"Osvaldo","family":"Ya\u00f1ez","sequence":"first","affiliation":[{"name":"Centro de Modelaci\u00f3n Ambiental y Din\u00e1mica de Sistemas (CEMADIS), Facultad de Ingenier\u00eda y Negocios, Universidad de Las Am\u00e9ricas  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2136-2305","authenticated-orcid":false,"given":"Daniel","family":"Bustos","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioinform\u00e1tica y Qu\u00edmica Computacional, Departamento de Medicina Traslacional, Facultad de Medicina Universidad Cat\u00f3lica del Maule  Talca Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisse","family":"Bravo","sequence":"additional","affiliation":[{"name":"Computational &amp; Quantum Enzyme Modeling Lab., Facultad de Odontolog\u00eda Universidad Andres Bello  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2448-9376","authenticated-orcid":false,"given":"Mat\u00edas","family":"Zu\u00f1iga\u2010Bustos","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Investigaci\u00f3n y Desarrollo Tecnol\u00f3gico Universidad Tecnol\u00f3gica Metropolitana  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1297-8351","authenticated-orcid":false,"given":"Manuel I.","family":"Osorio","sequence":"additional","affiliation":[{"name":"Computational &amp; Quantum Enzyme Modeling Lab., Facultad de Odontolog\u00eda Universidad Andres Bello  Santiago Chile"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica, Facultad de Medicina Universidad Diego Portales  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.13337"},{"key":"e_1_2_9_3_1","first-page":"1533","article-title":"Porphyromonas Gingivalis in the Development of Periodontitis: Impact on Dysbiosis and Inflammation","volume":"77","author":"Gasmi Benahmed A.","year":"2022","journal-title":"Archives of Razi Institute"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/s41522-021-00217-4","article-title":"Metabolic Plasticity Enables Lifestyle Transitions of \n                     Porphyromonas gingivalis","volume":"7","author":"Moradali M. 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