Computational Study of the Inhibition of RgpB Gingipain, a Promising Target for the Treatment of Alzheimer’s Disease
Impacte
Scholar |
Altres documents de l'autoria: Movilla Núñez, Santiago; Martí, Sergio; Roca, Maite; Moliner, Vicent
Metadades
Mostra el registre complet de l'elementcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/160292
comunitat-uji-handle3:10234/160293
comunitat-uji-handle4:
INVESTIGACIONMetadades
Títol
Computational Study of the Inhibition of RgpB Gingipain, a Promising Target for the Treatment of Alzheimer’s DiseaseData de publicació
2023-01-17Editor
American Chemical SocietyISSN
1549-9596; 1549-960XCita bibliogràfica
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).Tipus de document
info:eu-repo/semantics/articleVersió
info:eu-repo/semantics/publishedVersionParaules clau / Matèries
Resum
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 ... [+]
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. [-]
Publicat a
J. Chem. Inf. Model. 2023, 63, 3, 950–958Dades relacionades
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jcim.2c01198Entitat finançadora
Ministerio de Ciencia, Innovación y Universidades | Generalitat Valenciana | PROMETEO | Universitat Jaume I
Codi del projecte o subvenció
PGC2021-23332OB-C21 | CIPROM/2021/079 | UJI-2020-03 | UJI-2019-43 | GRISOLIAP/2019/064
Drets d'accés
© 2023 American Chemical Society
info:eu-repo/semantics/openAccess
info:eu-repo/semantics/openAccess
Apareix a les col.leccions
- INAM_Articles [519]