Standard Analysis

Each trajectory was subjected to a set of at least 32 analyses. Broadly the 32 analyses can be summarized as the analysis of gross structural changes (RMSD), assessment of secondary structural changes and calculation of number of contacts between residues, solvent accessible surface area (SASA) and Ramachandran distributions of residues. The set of analyses and the details of each calculation can be found in Table I.

Property	Subset	Method
Root-mean-squared deviations (RMSD)	Cα atoms from all residues	[1]
RMSD100	Cα RMSD normalized by that of a 100 residue protein	[2]
Structural dissimilarity (CONGENEAL)	Cα atoms from all residues	[3]
Solvent accessible surface area (SASA)	Non-polar Polar Main chain Main chain non-polar Main chain polar Side chain Side chain non-polar Side chain polar All residues	[4]
Heavy atom contacts	Non-polar Polar Other Main chain Side chain Native Non-native	X-X < 5.4 Å, where X is not charged Y-Y < 4.6 Å, where Y is charged X-Y < 4.6 Å, where X is not charged and Y is charged Z-Z, where Z is N,CA,C,O Z-Z, where Z is not N,CA,C,O Contacts present in the PDB structure Contacts not present in the PDB structure
Secondary structure by φ/ψ angles	Helix Beta-strand Extended Other	-100°<Φ<-30°, -80°<ψ<-5° [5] -170°<Φ<-50°, 80°<ψ<-170° [5] (Φ,ψ) within 20° of linear Not helix, beta or extended
Secondary Structure of Proteins (DSSP)	Helix Beta-strand Other/loop Alpha strand	[6] Alternating: -112°<Φ<-52°, -84°<ψ<-14° and 10°<Φ<80°, 52°<ψ<127° [7]
Nuclear magnetic resonance (NMR)	Nuclear Overhauser effects (NOE) Chemical shifts	Satisfied if the r-6 weighted mean distance was less than the experimental upper-bound or 5.0 Å, whichever was larger [8]

References

1. Kearsly SK. On the orthogonal transformation used for structural comparisons. Acta Crystallographica, A45: 208-210, 1989.
2. Carugo O., Pongor S. A normalized root-mean-square distance for comparing protein three-dimensional structures. Protein Science, 10:1470–1473, 2001.
3. Yee DP, Dill KA. Families and the structural relatedness among globular proteins. Protein Science, 2: 884-99, 1993
4. Lee B, Richards FM. Interpretation of protein structures: Estimation of static accessibility. Journal of Molecular Biology, 55: 379-400, 1971.
5. Daggett V, Kollman PA, Kuntz ID. A molecular dynamics simulation of polyalanine: An analysis of equilibrium motions and helix-coil transitions. Biopolymers, 31: 1115-1134, 1991.
6. Kabsch W, Sander C. Dictionary of protein secondary structure: Pattern-recognition of hydrogen-bonded and geometrical features. Biopolymers, 22: 2577-2637, 1983.
7. Daggett V. α-Sheet: The toxic conformer in amyloid diseases? Accounts of Chemical Research, 39: 594-602, 2006.
8. Osapay K, Case DA. A new analysis of proton chemical-shifts in proteins. Journal of the American Chemical Society, 113: 9436-9444, 1991.