| Texto completo | |
| Autor(es): |
de Oliveira, Osmair Vital
[1]
;
Goncalves, Arlan da Silva
[2]
;
Castilho de Almeida, Natalia Ellen
[3]
Número total de Autores: 3
|
| Afiliação do(s) autor(es): | [1] Inst Fed Educ Ciencia & Tecnol Sao Paulo, Campus Catanduva, BR-15808305 Catanduva, SP - Brazil
[2] Inst Fed Educ Ciencia & Tecnol Espirito Santo, Vila Velha, ES - Brazil
[3] Inst Fed Educ Ciencia & Tecnol Sao Paulo, Birigui, SP - Brazil
Número total de Afiliações: 3
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS; MAY 2021. |
| Citações Web of Science: | 0 |
| Resumo | |
In this study, comparable molecular dynamic (MD) simulations of 1.2 microseconds were performed to clarify the prevention of the beta-amyloid peptide (A beta(1-42)) aggregation by cucurbit{[}7]uril (CB{[}7]). The accumulation of this peptide in the brain is one of the most harmful in Alzheimer's disease. The inhibition mechanism of A beta(1-42) aggregation by different molecules is attributed to preventing of A beta(1-42) conformational transition from alpha-helix to the beta-sheet structure. However, our structural analysis shows that the pure water and aqueous solution of the CB{[}7] denature the native A beta(1-42) alpha-helix structure forming different compactness and unfolded conformations, not in beta-sheet form. On the other hand, in the three CB{[}7]@A beta(1-42) complexes, it was observed the encapsulation of N-terminal (Asp1), Lys16, and Val36 by CB{[}7] along the MD trajectory, and not with aromatic residues as suggested by the literature. Only in one CB{[}7]@A beta(1-42) complex was observed stable Asp23-Lys28 salt bridge with an average distance of 0.36 nm. All CB{[}7]@A beta(1-42) complexes are very stable with binding free energy lowest than similar to-50 kcal/mol between the CB{[}7] and A beta(1-42) monomer from MM/PBSA calculation. Therefore, herein we show that the mechanism of the prevention of elongation protofibril by CB{[}7] is due to the disruption of the Asp23-Lys28 salt bridge and steric effects of CB{[}7]@A beta(1-42) complex with the fibril lattice, and not due to the transition from alpha-helix to beta-sheet following the dock-lock mechanism. Communicated by Ramaswamy H. Sarma (AU) | |
| Processo FAPESP: | 18/19844-8 - Estudo Molecular do Encapsulamento de Compostos Bioativos na Cucurbit[7]urila |
| Beneficiário: | Osmair Vital de Oliveira |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |