Abstract
Combining structural proteomics experimental data with computational methods is a powerful tool for protein structure prediction. Here, we apply a recently-developed approach for de novo protein structure determination based on the incorporation of short-distance crosslinking data as constraints in discrete molecular dynamics simulations (CL-DMD) for the determination of conformational ensemble of the intrinsically disordered protein α-synuclein in the solution. The predicted structures were in agreement with hydrogen-deuterium exchange, circular dichroism, surface modification, and long-distance crosslinking data. We found that α-synuclein is present in solution as an ensemble of rather compact globular conformations with distinct topology and inter-residue contacts, which is well-represented by movements of the large loops and formation of few transient secondary structure elements. Non-amyloid component and C-terminal regions were consistently found to contain β-structure elements and hairpins.
Original language | English (US) |
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Article number | e1006859 |
Journal | PLoS computational biology |
Volume | 15 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2019 |
All Science Journal Classification (ASJC) codes
- Ecology, Evolution, Behavior and Systematics
- Modeling and Simulation
- Ecology
- Molecular Biology
- Genetics
- Cellular and Molecular Neuroscience
- Computational Theory and Mathematics