Fig 1.
Aβ10-40 sequence and conformations in different force fields.
(a) Aβ10-40 sequence is divided in four regions: hydrophilic N-terminal (S1, residues 10-16), central hydrophobic cluster (S2, residues 17-21), hydrophilic turn (S3, residues 22-28), and hydrophobic C-terminal (S4, residues 29-40). (b-f) Representative conformations of Aβ10-40 peptide in five force fields: (b) C36, (c) C36s, (d) C22*, (e) C22cmap, and (f) OPLS-AA. C36, C36s, and C22cmap structures in (b), (c), (e) show disordered peptide, whereas C22* in (d) and OPLS-AA in (f) structures illustrate helix or β propensities characterizing the respective force field. Side chains are colored to represent hydrophobic (in light grey), polar (in green), positively charged (in blue), and negatively charged (in red) residues. The backbone coloring follows the scheme used in (a).
Fig 2.
Aβ10-40 secondary structure in different force fields.
Total fractions of helix, turn, random coil, and β secondary structures for each of the five force fields probed in REMD simulations. All force fields predict dominance of turn and random coil conformations. C22* and OPLS-AA reveal moderate helix and β-structure propensities, respectively.
Fig 3.
Residue-specific Aβ10-40 secondary structure in different force fields.
Distributions of secondary structure in Aβ10-40 peptide with respect to sequence positions i for five force fields: (a) helix propensities 〈H(i)〉; (b) turn propensities 〈T(i)〉; (c) random coil propensities 〈RC(i)〉; (d) β propensities 〈S(i)〉. For clarity, sampling errors represented by vertical bars are shown for the C36 simulations only. Sequence regions are identified by the color scheme used in Fig 1a. C22* force field displays a significant helix structure in S3 and S4 regions, and the OPLS-AA system has a propensity for β-structure in S2 and S4.
Fig 4.
Aβ backbone fluctuations in different force fields.
Root-mean-square fluctuations (RMSF), δϕ(i) (black bars) and δψ(i) (red bars), in the backbone dihedral angles ϕ and ψ for Aβ10-40 amino acids i computed in five force fields: (a) C36, (b) C36s, (c) C22*, (d) C22cmap, and (e) OPLS-AA. Sampling errors are shown by vertical bars. Sequence regions are identified by the color scheme used in Fig 1a. The plots show that out of all force fields C22* predicts the most rigid backbone, especially in S2 and S4 regions.
Table 1.
Secondary Structure in Aβ10-40 Peptide.
Fig 5.
Aβ10-40 tertiary interactions in different force fields.
Intrapeptide contact maps, 〈C(i, j)〉, present the probabilities of forming contacts between residues i and j in Aβ10-40 peptide for five force fields: (a) C36, (b) C36s, (c) C22*, (d) C22cmap [44], and (e) OPLS-AA. The bars on the right-side color code 〈C(i, j)〉 values. Sequence regions are identified by the color scheme used in Fig 1a. C36, C36s, and C22cmap contact maps reveal lack of stable long-range interactions, whereas C22* displays few exceptionally strong long- and short-range contacts. OPLS-AA contact map is characterized by extensive but flickering tertiary interactions.
Table 2.
Five top side chain contacts in Aβ10-40 peptide for C36 force field.
Fig 6.
Aβ radius of gyration in different force fields.
Probability distributions, P(Rg), for the radius of gyration Rg of Aβ10-40 peptide computed for five force fields. Vertical bars represent sampling errors. The plots show that, in contrast to C36, C36s, and C22cmap force fields, C22* and OPLS-AA predict collapsed peptide structures.
Table 3.
Five top side chain contacts in Aβ10-40 peptide for C36s force field.
Table 4.
Five top side chain contacts in Aβ10-40 peptide for C22* force field.
Table 5.
Five top side chain contacts in Aβ10-40 peptide for C22cmap force fielda.
Table 6.
Five top side chain contacts in Aβ10-40 peptide for OPLS-AA force field.
Fig 7.
Comparison of in silico and experimental structural data.
(a) Distributions of 3JHNHα-coupling constants, Jcomp(i), computed for Aβ10-40 peptide using Pardi et al coefficients for Karplus equation [51] and REMD sampling generated with five force fields. Superimposed are experimental 3JHNHα-coupling constants, Jexp(i) (black lines with circles) measured by Roche et al [18]. This combination of Karplus equation coefficients and experimental data provides the best agreement between Jcomp(i) and Jexp(i). Only amino acids with experimentally available data are considered. (b) Distributions of RDC constants computed for Aβ10-40 peptide using PALES program [55] and REMD sampling generated with five force fields. Superimposed are experimental RDC constants (black lines with circles) measured by Wang and coworkers [54].
Table 7.
Comparison of experimental and computational J-coupling and RDC constants†.