期刊
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
卷 19, 期 -, 页码 1595-1602出版社
ELSEVIER
DOI: 10.1016/j.csbj.2021.02.014
关键词
Polyglutamine diseases; Peptide aggregation; Toxic oligomers; Molecular dynamics; Coarse grained modelling
资金
- FOCEM [COF 03/11]
- National Natural Science Foundation of China (NSFC) [31770776]
Poly glutamine and glutamine-rich peptides are central in pathological aggregation events, their biophysical properties can be characterized using coarse-grained simulations. A double role for glutamines was found in the study, mediating seeding and optimizing hydrogen bond networks for aggregates maturation.
Poly glutamine and glutamine-rich peptides play a central role in a plethora of pathological aggregation events. However, biophysical characterization of soluble oligomers-the most toxic species involved in these processes-remains elusive due to their structural heterogeneity and dynamical nature. Here, we exploit the high spatio-temporal resolution of coarse-grained simulations as a computational microscope to characterize the aggregation propensity and morphology of a series of polyglutamine and glutaminerich peptides. Comparative analysis of ab-initio aggregation pinpointed a double role for glutamines. In the first phase, glutamines mediate seeding by pairing monomeric peptides, which serve as primers for higher-order nucleation. According to the glutamine content, these low molecular-weight oligomers may then proceed to create larger aggregates. Once within the aggregates, buried glutamines continue to play a role in their maturation by optimizing solvent-protected hydrogen bonds networks. (C) 2021 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
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