Table 1.

Description of the systems, parameterization and trajectory lengths simulated in this work, together with a brief description of the key observations compared to the behavior expected based on experimental knowledge of the different systems.

System	Parameterization(protein-water)	Replicas × length	Expected behavior (italics) vs. observations in the simulations
Single Htt-1-19 peptide in 100 mM KCl at neutral pH			Soluble and disordered but with ~10–30% helical propensity according to circular dichroism spectra that peaks at residues 14–18[45].
	ff14SB-TIP3P	1 × ~ 10 µs	Helix propensity too high (45%), highest for residues 3–12.
	CHARMM36m-TIP3P*	1 × ~ 10 µs	22% helix propensity, highest for residues 9–15.
	a99SBdisp-TIP4PD	1 × ~ 10 µs	28% helix propensity, highest for residues 3–14.
	ff19SB-OPC	1 × ~ 10 µs	29% helix propensity, highest for residues 4–11.
3 ubiquitin molecules around 5 mM, in 100 mM KCl at neutral pH			Soluble but undergoing weak dimerization through a favored interface (residues 4–12, 42–51 and 62–71), exchanging in the microsecond timescale[40].
	ff14SB-TIP3P	3 × ~ 1.7 µs	Aggregation into dimers and then trimers that get increasingly more compact.
	CHARMM36m-TIP3P*	3 × ~ 2 µs	Aggregation into dimers and then trimers but less compact than with ff14SB-TIP3P.
	a99SBdisp-TIP4PD	3 × ~ 1.9 µs	Soluble with a few short-lived encounters that do not match the NMR data; no trimers.
	ff19SB-OPC	3 × ~ 2.2 us	Dimers lasting for tens to few hundreds nanoseconds, contacts most consistent with NMR data yet not perfect; no trimers.
9 ubiquitin molecules around 5 mM, in 100 mM KCl at neutral pH			Soluble but undergoing weak dimerization through a favored interface (residues 4–12, 42–51 and 62–71), exchanging in the microsecond timescale[40].
	ff14SB-TIP3P	1 × ~ 0.95 µs	Aggregates form and grow bigger and more compact.
	CHARMM36m-TIP3P*	1 ×  ~ 0.88 µs	Aggregates form and grow bigger, but less compact than ff14SB-TIP3P.
	a99SBdisp-TIP4PD	1 ×  ~ 1.1 µs	Highly soluble, only collisions through no preferred surface.
	ff19SB-OPC	1 ×  ~ 1.1 us	Some dimers form that then grow into bigger aggregates, but slower than C36m.
10 Aβ 16–22 molecules at around 10 mM, in 50 mM KCl at neutral pH			Totally insoluble in water. Forms β-rich fibrils and amorphous aggregates depending on conditions and concentration[41].
	ff14SB-TIP3P	1 ×  ~ 1.8 µs	Aggregate of large β content
	CHARMM36m-TIP3P*	1 ×  ~ 1.8 µs	Aggregate of large β content
	a99SBdisp-TIP4PD	1 ×  ~ 2 µs	Remains soluble, some reversible formation of different pairs of strands
	ff19SB-OPC	1 × 1.95 us	Largely soluble, with small aggregates of β content
Fiber stretch of 10 Aβ-40 strands from PDB 2LNQ, in 50 mM KCl at neutral pH			Totally insoluble fiber that does not dissociate in water[51].
	ff14SB-TIP3P	3 ×  ~ 3 µs	Rigid, max Cα RMSD 5–6 Å
	CHARMM36m-TIP3P*	3 ×  ~ 3 µs	Less rigid than ff14SB, max Cα RMSD 8–10 Å.
	a99SBdisp-TIP4PD	3 ×  ~ 3 µs	Similar to CHARMM36m, max Cα RMSD 8–10 Å.
	ff19SB-OPC	3 ×  ~ 3 us	As rigid as ff14SB-TIP3P, max Cα RMSD 5–6 Å