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Computational Study of the Inhibition of RgpB Gingipain, a Promising Target for the Treatment of Alzheimer’s Disease
dc.contributor.author | Movilla Núñez, Santiago | |
dc.contributor.author | Martí, Sergio | |
dc.contributor.author | Roca, Maite | |
dc.contributor.author | Moliner, Vicent | |
dc.date.accessioned | 2023-06-16T09:53:47Z | |
dc.date.available | 2023-06-16T09:53:47Z | |
dc.date.issued | 2023-01-17 | |
dc.identifier.citation | Movilla, Santiago, et al. "Computational Study of the Inhibition of RgpB Gingipain, a Promising Target for the Treatment of Alzheimer’s Disease." Journal of Chemical Information and Modeling (2023). | ca_CA |
dc.identifier.issn | 1549-9596 | |
dc.identifier.issn | 1549-960X | |
dc.identifier.uri | http://hdl.handle.net/10234/202871 | |
dc.description.abstract | Alzheimer’s disease represents one of the most ambitious challenges for biomedical sciences due to the growing number of cases worldwide in the elderly population and the lack of efficient treatments. One of the recent attempts to develop a treatment points to the cysteine protease RgpB as a promising drug target. In this attempt, several small-molecule covalent inhibitors of this enzyme have been proposed. Here, we report a computational study at the atomic level of the inhibition mechanism of the most promising reported compounds. Molecular dynamics simulations were performed on six of them, and their binding energies in the active site of the protein were computed. Contact maps and interaction energies were decomposed by residues to disclose those key interactions with the enzyme. Finally, quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations were performed to evaluate the reaction mechanism by which these drug candidates lead to covalently bound complexes, inhibiting the RgpB protease. The results provide a guide for future re-design of prospective and efficient inhibitors for the treatment of Alzheimer’s disease. | ca_CA |
dc.description.sponsorShip | Funding for open access charge: CRUE-Universitat Jaume I | |
dc.format.extent | 9 p. | ca_CA |
dc.format.mimetype | application/pdf | ca_CA |
dc.language.iso | eng | ca_CA |
dc.publisher | American Chemical Society | ca_CA |
dc.relation.isPartOf | J. Chem. Inf. Model. 2023, 63, 3, 950–958 | ca_CA |
dc.relation.uri | The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jcim.2c01198 | ca_CA |
dc.rights | © 2023 American Chemical Society | ca_CA |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | ca_CA |
dc.subject | free energy | ca_CA |
dc.subject | inhibitors | ca_CA |
dc.subject | molecules | ca_CA |
dc.subject | peptides and proteins | ca_CA |
dc.subject | reaction mechanisms | ca_CA |
dc.title | Computational Study of the Inhibition of RgpB Gingipain, a Promising Target for the Treatment of Alzheimer’s Disease | ca_CA |
dc.type | info:eu-repo/semantics/article | ca_CA |
dc.identifier.doi | 10.1021/acs.jcim.2c01198 | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | ca_CA |
dc.type.version | info:eu-repo/semantics/publishedVersion | ca_CA |
project.funder.name | Ministerio de Ciencia, Innovación y Universidades | ca_CA |
project.funder.name | Generalitat Valenciana | ca_CA |
project.funder.name | PROMETEO | ca_CA |
project.funder.name | Universitat Jaume I | ca_CA |
oaire.awardNumber | PGC2021-23332OB-C21 | ca_CA |
oaire.awardNumber | CIPROM/2021/079 | ca_CA |
oaire.awardNumber | UJI-2020-03 | ca_CA |
oaire.awardNumber | UJI-2019-43 | ca_CA |
oaire.awardNumber | GRISOLIAP/2019/064 | ca_CA |
dc.subject.ods | 3. Salud y bienestar |
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