| Full text | |
| Author(s): |
Sanches, Murilo N.
[1]
;
Knapp, Kaitlin
[2]
;
Oliveira, Antonio B.
[2]
;
Wolynes, Peter G.
[2]
;
Onuchic, Jose N.
[3, 2, 4, 5]
;
Leite, Vitor B. P.
[1]
Total Authors: 6
|
| Affiliation: | [1] Sao Paulo State Univ UNESP, Inst Biosci Humanities & Exact Sci, Dept Phys, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
[2] Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 - USA
[3] Rice Univ, Dept Chem, Houston, TX 77005 - USA
[4] Rice Univ, Dept Biosci, Houston, TX 77005 - USA
[5] Rice Univ, Dept Phys & Astron, Houston, TX 77005 - USA
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | Journal of Physical Chemistry B; DEC 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
The amyloid-fl (Afl) monomer, an intrinsically disordered peptide, is produced by the cleavage of the amyloid precursor protein, leading to Afl-40 and Afl-42 as major products. These two isoforms generate pathological aggregates, whose accumulation correlates with Alzheimer's disease (AD). Experiments have shown that even though the natural abundance of Afl-42 is smaller than that for Afl-40, the Afl-42 is more aggregation-prone compared to Afl-40. Moreover, several single-point mutations are associated with early onset forms of AD. This work analyzes coarse-grained associative-memory, water-mediated, structure and energy model (AWSEM) simulations of normal Afl-40 and Afl-42 monomers, along with six single-point mutations associated with early onset disease. We analyzed the simulations using the energy landscape visualization method (ELViM), a reactioncoordinate-free approach suited to explore the frustrated energy landscapes of intrinsically disordered proteins. ELViM is shown to distinguish the monomer ensembles of variants that rapidly form fibers from those that do not form fibers as readily. It also delineates the amino acid contacts characterizing each ensemble. The results shed light on the potential of ELViM to probe intrinsically disordered proteins. (AU) | |
| FAPESP's process: | 18/18668-1 - Biological macromolecules energy landscapes visualization |
| Grantee: | Vitor Barbanti Pereira Leite |
| Support Opportunities: | Scholarships abroad - Research |
| FAPESP's process: | 19/22540-3 - Studies of energy landscapes of biological macromolecules |
| Grantee: | Vitor Barbanti Pereira Leite |
| Support Opportunities: | Regular Research Grants |