TABLE 1.

Reported experimental and computational data on monomeric wt αSyn.

Structural features		Technique		References
Global	Local	Experimental	Computational
Compact, globular structure Electrostatic interactions (120–140 and 30–100 residues)	–	Technique: PRE1	Technique: MD2	Dedmon et al. (2005a)
		Spin label MTSL
		Cysteine mutations at Q24, S42, Q62, S87 and N103
Brief long-range intramolecular electrostatic interactions	–	Technique: NMR3	–	Bertoncini et al. (2005)
		100uM WT αSyn in buffer (25mM Tris.Cl pH = 7.4/0.1M NaCl)
Extended tendency	N-terminal: Helical elements	Technique: NMR3	Technique: restrained MD2	Allison et al., 2009
Brief long-range intramolecular electrostatic interactions			Solvent: implicit
Compact structure at both neutral and low pH	–	Technique: PRE1	–	Wu and Baum, (2010)
C- to N-terminal interchain interactions		Various pH, concentrations, solvents
Compact structure (low pH)	–	Technique: Single-Molecule FRET4	Technique: constrained excluded volume MC5	Nath et al. (2012)
		50 pM solution of double-labeled WT αSyn	Technique: All-atom MD2
			Solvent: explicit
High-energy phase: Extended random coil Low-energy phase: Extended all-β	High-energy phase:	–	Technique: MC5	Jónsson et al. (2012)
	N-terminal: Helical elements		Solvent: Implicit
	Low-energy phase:
	N-terminal + NAC + C-terminal (residues 30–100): β-strands
	C-terminal: β-structures + random coil
–	N-terminal + NAC + C-terminal (residues 1–100): Helical elements	–	Technique: REMD6	Coskuner et al., (2013)
			Solvents: implicit
			Technique: MD2
			Solvents: explicit
Compact structure	N-terminal: Helical elements + β-hairpin spanning residues 38–53	–	Technique: coarse-grained MD2	Yu et al. (2015)
Electrostatic interactions (118–130 and 38–53 residues)	β-strands: β1 (38–44) and β2 (47–53)		Solvent: explicit
α+β	NAC: Helical elements
	C-terminal: Helical elements + β-structures
Compact, globular structure	N-terminal: Helical elements	Technique: HS-AFM7	Technique: REX8/DMD9	Zhang et al. (2018)
Tail-like protrusions	NAC: Helical elements	50nM WT αSyn in PBS	Solvent: Lazaridis-Karplus implicit
All-α	C-terminal: Helical elements
Compact, globular structure	N-terminal: Helical elements spanning residues 25–55	Techniques:	Technique: REX8/DMD9	Brodie et al., 2019
Brief long-range intramolecular	NAC: β-structures	LD-CL10, CD11,HDX12,	Solvent: Lazaridis-Karplus implicit
electrostatic interactions α+β	C-terminal: β-structures + random coil	LC-MS13/MS Analysis
Compact, globular structure	N-terminal: Helical elements	–	Technique: MD2	Bhattacharya et al. (2019)
Tail-like protrusions	NAC: Helical elements		Solvents: explicit
All-α	C-terminal: Helical elements + random coil
–	N-terminal: Helical elements spanning residues 10–30 and a weak helix centered around residue 50	Technique: NMR3	–	Kim et al. (2020) (review)
	NAC: tendency to form β-structures helix centered around residue 90

¹Paramagnetic Relaxation Enhancement.

²Molecular Dynamics simulations.

³Nuclear magnetic resonance.

⁴Fluorescence resonance energy transfer.

⁵Monte Carlo simulations.

⁶Replica Exchange Molecular Dynamics simulations.

⁷High-Speed Atomic Force Microscopy.

⁸All-atom Replica Exchange.

⁹Discrete Molecular Dynamics.

¹⁰Long-distance crosslinking.

¹¹Circular dichroism.

¹²Hydrogen-deuterium exchange.

¹³Liquid chromatography–mass spectrometry.