Artículos de revistas
Conformational transition of Aβ42 inhibited by a mimetic peptide. A molecular modeling study using QM/MM calculations and QTAIM analysis
Fecha
2016-03Registro en:
Barrera Guisasola, Exequiel Ernesto; Gutierrez, Lucas Joel; Salcedo, Rodrigo Emiliano; Garibotto, Francisco Matías; Andujar, Sebastian Antonio; et al.; Conformational transition of Aβ42 inhibited by a mimetic peptide. A molecular modeling study using QM/MM calculations and QTAIM analysis; Elsevier; Computational and Theoretical Chemistry; 1080; 3-2016; 56-65
2210-271X
CONICET Digital
CONICET
Autor
Barrera Guisasola, Exequiel Ernesto
Gutierrez, Lucas Joel
Salcedo, Rodrigo Emiliano
Garibotto, Francisco Matías
Andujar, Sebastian Antonio
Enriz, Ricardo Daniel
Rodríguez, Ana M.
Resumen
The main pathogenic event in Alzheimer's disease is believed to be the aggregation of the amyloid β-peptides into toxic aggregates. In a previous work we designed a mimetic peptide possessing a significant aggregation modulating effect by means of a molecular modeling study, using a pentameric model as a molecular target. Considerable experimental evidence indicates that oligomers as small as dimers have been involved in this disease. Therefore, an alternative therapeutic strategy might be to block the oligomerization at a monomeric level. To this end, using an Aβ42 monomeric model, we explored the capacity and mechanism of our mimetic peptides to stabilize the α-helical conformation while preventing the formation of β-sheet structures. Long time molecular dynamics simulations and MM-GBSA analysis were coupled to investigate this issue. In addition, a combined ONIOM-QTAIM analysis was used to identify at a quantum level the most relevant interactions between Aβ42 and this inhibitor. The computational analysis presented here pointed out six important residues of Aβ42 (Lys16, Val36, Gly37, Gly38, Val39 and Val40) that strongly interact with our mimetic peptide, providing clues about the functional groups that might be modified in order to obtain more potent inhibitors.