Year: 2024
Type: review
Abstract: Protein self-assembly plays an important role in biological systems, accounting for the formation of mesoscopic structures that can be highly symmetric as in the capsid of viruses or disordered as in molecular condensates or exhibit a one-dimensional fibrillar morphology as in amyloid fibrils. Deposits of the latter in tissues of individuals with degenerative diseases like Alzheimer's and Parkinson's has motivated extensive efforts to understand the sequence of molecular events accounting for their formation. These studies aim to identify on-pathway intermediates that may be the targets for therapeutic intervention. This detailed knowledge of fibril formation remains obscure, in part due to challenges with experimental analyses of these processes. However, important progress is being achieved for short amyloid peptides due to advances in our ability to perform completely unbiased all-atom simulations of the self-assembly process. This perspective discusses recent developments, their implications, and the hurdles that still need to be overcome to further advance the field.
Institutions: University of Rochester, New Jersey Institute of Technology
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: G2683939444, Collaborative Research: Supramolecular Multi-Component Peptide Nanofibrils: Bridging Understanding at Atomic and Mesoscopic Scales with Structure and Theory, Collaborative Research: Supramolecular Multi-Component Peptide Nanofibrils: Bridging Understanding at Atomic and Mesoscopic Scales with Structure and Theory, G6891019700, Elucidating the sequence code for amyloid peptide self-assembly through all-atom simulations, machine learning, and experiments
OpenAlex ID: W4392498699