Supporting Information
Characterizing Amyloid-beta Protein Misfolding from Molecular
Dynamics Simulations with Explicit Water
Chewook Lee and Sihyun Ham*
Department of Chemistry, Sookmyung Women’s University
Hyochangwon-gil 52, Yongsan-gu, Seoul, 140-742, Korea
1. Comparison between simulated and experimental NMR J-coupling Constants·····2
2. Representative Structures from ten MD Trajectories·····································3
3. Various Aggregation-Prone Structures·······················································4
4. Sequence of Aß42 Misfolding Events in Water··············································7
1
1. Comparison between Simulated and Experimental NMR J-coupling Constants
Figure S1. Computed three bonds (HN-N-C-H) J-coupling constants (filled circle) from MD
simulations are compared with the NMR experimental values (open circle) from Ref. 51.
Computed values were obtained based on the selected ten clusters sampled by the clustering
analysis for 500 ns MD trajectories. The average value of the calculated J-coupling constants
for Aß42 is 6.65 with a standard deviation of 0.94. The average value of the reported
experimental J-coupling constants is 6.80 with a standard deviation of 0.74. We also calculated
the Pearson’s correlation coefficient (PCC), i.e. the absolute deviation from experimental
values over the sum of errors to evaluate the correlation between the calculated and
experimental J-coupling constant values. The calculated PCC value based on our simulation
results is 0.39. Previously reported PCC value for Aß42 in the Ref. 51 is 0.43 using OPLS force
field. Nevertheless, the force field used for these simulations qualitatively reproduces the
experimentally determined NMR J-coupling constants but somewhat underestimate the values
of J-coupling constants, which is in agreement with the previous observation.
2
2. Representative Structures from Ten MD Trajectories
Traj. A
Traj. B
Traj. C
Traj. D
Traj. E
Traj. F
Traj. G
Traj. H
Traj. I
Traj. J
Figure S2. The most populated structures for Aß42 in water obtained from ten independent trajectories. Each structure is the closest
one to the centroid of the largest conformational cluster. The structures are color-coded according to sequence, ranging from blue to
red at the N- and C-termini, respectively.
3
3. Various Aggregation-Prone Structures
Table S1. Various structural factors of aggregation-prone structures.
# of
Structure
C
RMSDa
Radius of
Gyrationb
SASAc
Variation
C
Contactd
Nonlocal
Backbone
Contacth
1
8.653
11.994
18.37
59.45
20.19
10.385
20.967
59.56
(0.373)
(0.168)
(5.41)
(3.06)
(2.83)
(0.316)
(1.496)
(7.97)
2
8.854
11.976
20.34
60.21
18.75
10.428
21.431
50.21
(0.337)
(0.180)
(6.39)
(3.18)
(2.11)
(0.362)
(1.358)
(17.48)
3
11.136
11.177
5.76
55.16
19.24
9.001
15.115
28.55
(0.267)
(0.166)
(5.60)
(4.76)
(3.74)
(0.277)
(2.108)
(13.60)
4
10.242
10.447
12.04
62.92
23.55
11.391
22.137
25.13
(0.166)
(0.124)
(5.66)
(3.51)
(2.02)
(0.322)
(1.839)
(5.52)
5
10.312
10.652
10.23
57.97
24.61
12.242
21.879
7.62
(0.239)
(0.152)
(6.30)
(3.21)
(1.82)
(0.367)
(1.792)
(5.20)
6
10.997
10.484
13.52
64.67
20.69
11.241
19.730
25.78
(0.236)
(0.201)
(5.21)
(2.59)
(1.61)
(0.208)
(1.107)
(4.07)
7
11.360
9.718
6.29
59.66
15.39
8.612
18.435
60.28
(0.127)
(0.077)
(5.12)
(2.98)
(1.25)
(0.290)
(0.903)
(13.12)
8
11.233
9.797
6.64
55.37
14.99
8.863
18.689
44.41
(0.127)
(0.109)
(5.59)
(4.23)
(1.79)
(0.345)
(1.278)
(16.96)
Av.
10.348
10.781
11.65
59.43
19.68
10.270
19.798
37.69
(0.234)
(0.147)
(5.66)
(2.15)
(2.15)
(0.311)
(1.485)
(10.49)
a) Root-mean-square deviation of C atoms of 42 residues (unit: Å), b) unit : Å, c) variation of solvent accessible surface area (SASA)
for hydrophobic residues with respect to the initial structure, (water probe: 1.4 Å, unit: %), d) number of contact between Cα atoms
within 6.5 Å, e) number of hydrophobic contacts between residues within 5.4 Å, (hydrophobic residues are listed in the subsection,
Trajectory analysis), f) the distance between the center of mass of Aß(17-26) and Aß(33-42) (unit: Å), g) end-to-end distance between
Cα atoms in both termini. (unit: Å), h) nonlocal backbone heavy atom contact within 5.4 Å between Aß(15-25) and Aß(32-42).
4
Tertiary
Contacte
HP core
Distancef
End-to-End
Distanceg
1
2
3
4
5
6
7
8
Figure S3. Various aggregation-prone structures for A42 in water. The structures are color-coded according to sequence, ranging
from blue to red at the N- and C-termini, respectively.
5
1
2
3
4
5
6
7
8
Figure S4. Average contact maps of eight aggregation-prone structures of Aß42 which are corresponded to the structures in Figure S3,
respectively. Black dot denotes the distance between two closest heavy atoms of the two residues is within 3.0 Å and white area
represents the distance over 7.0 Å. Values in between are shown with increasing levels of gray. Backbone contacts are shown in leftupper side and side chain contacts are shown in right-lower side in each figure.
6
4. Sequence of Aß42 Misfolding Events in Water
Figure S5. Sequence of hierarchical events of Aß42 monomer misfolding: 0 ns: initial
helix-kink-helix, 2 ns and 7 ns: hydrophobic C-terminal fluctuation, 18 ns: loop
formation (res. 25-29) and 24 ns: central hydrophobic core regions (res. 17-21) and Cterminal region (res. 38-42) get closer and nonlocal backbone contact are formed, 43
ns: the number of nonlocal backbone contact gets increased, and the hydrophobic
solvent accessible surface area gets increased, and 50 ns: tight backbone H-bonding
formation is observed. The structures are color-coded according to sequence, ranging
from blue to red at the N- and C-termini, respectively.
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