Insight into the stability of cross‐β amyloid fibril from molecular dynamics simulation

Abstract

Amyloid fibrils are considered to play causal roles in the pathogenesis of amyloid-related degenerative diseases such as Alzheimer's disease, type II diabetes mellitus, the transmissible spongiform encephalopathies, and prion disease. The mechanism of fibril formation is still hotly debated and remains an important open question. In this study, we utilized molecular dynamics (MD) simulation to analyze the stability of hexamer for eight class peptides. The MD results suggest that VEALYL and MVGGVV-1 are the most stable ones, then SNQNNY, followed by LYQLEN, MVGGVV-2, VQIVYK, SSTSAA, and GGVVIA. The statistics result indicates that hydrophobic residues play a key role in stabilizing the zipper interface. Single point and two linkage mutants of MVGGVV-1 confirmed that both Met1 and Val2 are key hydrophobic residues. This is consistent with the statistics analysis. The stability results of oligomer for MVGGVV-1 suggest that the intermediate state should be trimer (3-0) and tetramer (2-2). These methods can be used in stabilization study of other amyloid fibril.

Kink turn sRNA folding upon L7Ae binding using molecular dynamics simulations

“…[52][53][54][55][56][57][58][59][60][61] Residues and nucleotides are in hydrophobic contact when mass centers of their side chains are closer than 6.5 Å for the complex. A previous study has shown that charge-to-charge interactions of up to 11 Å were found to contribute to protein-RNA binding free energies.…”

Insight into the Stability of Cross-β Amyloid Fibril from VEALYL Short Peptide with Molecular Dynamics Simulation

“…The MD results suggest that VEALYL and MVGGVV-1 are the most stable ones. Then we study the aggregation mechanism of MVGGVV-1 amyloid fibrils [30]. The results indicate that the study of short peptide aggregation could reveal some common fundamental mechanisms for the fibril formation in large protein systems.…”

Role of D278N mutation for stability of prion dimer and tetramer structure

“…Interactions of prion dimers and the formation of β-sheets may be a first step in cross-β-sheet formation leading to fibrillation, as found in amyloid fibril in Alzheimer's disease studied by X-ray diffraction [5]. The mechanism of amyloid formation [6] and the effects of mutations on prion misfolding have also been widely investigated using molecular dynamics (MD) simulations [7][8][9]. A particular mutation related to hereditary familial prion disease and fatal familial insomnia is D178N.…”