{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T05:39:44Z","timestamp":1775885984319,"version":"3.50.1"},"reference-count":76,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/137844\/2018, UIDP\/04378\/2020, UIDB\/04378\/2020 and 2020.01423.CEECIND\/CP1596\/CT0003"],"award-info":[{"award-number":["SFRH\/BD\/137844\/2018, UIDP\/04378\/2020, UIDB\/04378\/2020 and 2020.01423.CEECIND\/CP1596\/CT0003"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>With tuberculosis still being one of leading causes of death in the world and the emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb), researchers have been seeking to find further therapeutic strategies or more specific molecular targets. PknB is one of the 11 Ser\/Thr protein kinases of Mtb and is responsible for phosphorylation-mediated signaling, mainly involved in cell wall synthesis, cell division and metabolism. With the amount of structural information available and the great interest in protein kinases, PknB has become an attractive target for drug development. This work describes the optimization and application of an in silico computational protocol to find new PknB inhibitors. This multi-level computational approach combines protein\u2013ligand docking, structure-based virtual screening, molecular dynamics simulations and free energy calculations. The optimized protocol was applied to screen a large dataset containing 129,650 molecules, obtained from the ZINC\/FDA-Approved database, Mu.Ta.Lig Virtual Chemotheca and Chimioth\u00e8que Nationale. It was observed that the most promising compounds selected occupy the adenine-binding pocket in PknB, and the main interacting residues are Leu17, Val26, Tyr94 and Met155. Only one of the compounds was able to move the active site residues into an open conformation. It was also observed that the P-loop and magnesium position loops change according to the characteristics of the ligand. This protocol led to the identification of six compounds for further experimental testing while also providing additional structural information for the design of more specific and more effective derivatives.<\/jats:p>","DOI":"10.3390\/molecules26206162","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T06:38:41Z","timestamp":1634107121000},"page":"6162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["In Silico Identification of Possible Inhibitors for Protein Kinase B (PknB) of Mycobacterium tuberculosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5137-0798","authenticated-orcid":false,"given":"Tatiana F.","family":"Vieira","sequence":"first","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, BioSIM-Departamento de Biomedicina, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6257-8885","authenticated-orcid":false,"given":"F\u00e1bio G.","family":"Martins","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, BioSIM-Departamento de Biomedicina, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"}]},{"given":"Joel P.","family":"Moreira","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, BioSIM-Departamento de Biomedicina, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"}]},{"given":"Tiago","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, BioSIM-Departamento de Biomedicina, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6560-5284","authenticated-orcid":false,"given":"S\u00e9rgio F.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, BioSIM-Departamento de Biomedicina, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13858","DOI":"10.1074\/jbc.M114.563536","article-title":"Protein Kinase B (PknB) of Mycobacterium tuberculosis Is Essential for Growth of the Pathogen in Vitro as well as for Survival within the Host","volume":"289","author":"Chawla","year":"2014","journal-title":"J. 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