Supplementary Figure Legends
Figure S1 VLB geometry in (A) crystal structure of 4EB6 and (B) the first rate docking solution.
Some interacting residues from α-tubulin (yellow) and β-tubulin (green) are shown at the binding
pocket. (C) Front and (D) back view of the 1st rate (grey) and 6th rate (green) docking poses.
The protonated nitrogen is highlighted in a sphere.
Figure S2 Helicity plots of H3, the new helix formed at T7 loop, H10 and H11 in α-tubulin
comparing the unliganded and liganded system at 300 K.
Figure S3 Helicity plots of H5 in β-tubulin comparing the unliganded and liganded system at
300 K.
Figure S4 Helicity plots of H3, H5, the new helix formed at T7 loop, H10 and H11 in α-tubulin
comparing the unliganded system at 300 K and 277 K, respectively.
Figure S5 Helicity plots of H3, H5 and H7 in β-tubulin comparing the unliganded system at 300
K and 277 K, respectively.
Figure S6 SASA of α- and β-tubulin in three systems at the 2nd round simulations changing
over the 115 ns simulation time.
S1
Figure S7 The curvature of αβ-tubulin heterodimer represented by H7 orientation of the
unliganded heterodimer at (A) 300 K, (B) 277 K and of (C) the liganded heterodimer at 300 K
from the 2nd round simulations. The angles indicate the average deviation of heterodimers
shifting from the curved conformation in the crystal structure. The inset scheme at (C) describes
the structure caused by VLB with more bending than the crystal structure.
Figure S8 The distance between charged residues contributing to the electrostatic surface. Each
panel is a comparison of a pair of charged residues under two different conditions. The dashed
line indicates convergence point.
Figure S9 Helicity plots of H3, the new helix formed at T7 loop, H10 and H11 in α-tubulin
comparing the unliganded and liganded system at 300 K. The left is from the first round
simulations and the right is from the second round simulations. (same as below)
Figure S10 Helicity plots of H5 in β-tubulin comparing the unliganded and liganded system at
300 K.
Figure S11 Helicity plots of H3, the new helix formed at T7 loop and H10 in α-tubulin
comparing the unliganded system at 300 K and 277 K, respectively.
S2
Figure S12 Helicity plots of H3 and H7 in β-tubulin comparing the unliganded system at 300 K
and 277 K, respectively.
S3
Supplementary Tables
Tables
Table S1 The top 10 docking solutions of mono-protonated VLB ranked by FlexX.
Score
Match
Lipophilic Ambiguous
(kJ/mol) (kJ/mol) (kJ/mol)
(kJ/mol)
-8.0814 -13.0764 -13.542
-8.5235
1
2
-6.2647 -14.7242 -11.4641 -9.289
3
-6.1923 -15.6398 -12.7842 -9.3892
4
-5.3067 -15.6806 -13.5578 -9.0258
5
-4.4144 -12.9817 -16.1357 -9.473
-3.7758 -10.6882 -12.59
-7.3485
6
7
-3.4799 -12.7875 -13.0774 -7.8528
8
-3.3683 -15.5418 -9.7845
-8.9348
9
-2.0776 -15.5224 -13.6993 -8.3718
10
-1.9751 -10.7183 -11.3053 -6.2374
Score: total score of the docking solution
rank
Clash
(kJ/mol)
4.8606
7.0126
9.4209
10.7575
11.9761
4.6505
8.0378
8.6928
13.3159
4.0859
RMSD
(Å)
6.3851
10.7734
8.6124
8.1732
7.5182
6.3335
8.3967
9.1038
7.4438
8.8255
Match: contribution of the matched interacting groups
Lipophilic: contribution of the lipophilic contact area
Ambiguous: contribution of the lipophilic-hydrophilic (ambiguous) contact area
Clash: contribution of the clash penalty
RMSD: RMSD of coordinates from reference coordinates
S4
Figures
Figure S1 VLB geometry in (A) crystal structure of 4EB6 and (B) the first rate docking solution.
Some interacting residues from α-tubulin (yellow) and β-tubulin (green) are shown at the binding
pocket. (C) Front and (D) back view of the 1st rate (grey) and 6th rate (green) docking poses.
The protonated nitrogen is highlighted in a sphere.
S5
Figure S2 Helicity plots of H3, the new helix formed at T7 loop, H10 and H11 in α-tubulin
comparing the unliganded and liganded system at 300 K.
S6
Figure S3 Helicity plots of H5 in β-tubulin comparing the unliganded and liganded system at
300 K.
S7
Figure S4 Helicity plots of H3, H5, the new helix formed at T7 loop, H10 and H11 in α-tubulin
comparing the unliganded system at 300 K and 277 K, respectively.
S8
Figure S5 Helicity plots of H3, H5 and H7 in β-tubulin comparing the unliganded system at 300
K and 277 K, respectively.
S9
Figure S6 SASA of α- and β-tubulin in three systems at the 2nd round simulations changing
over the 115 ns simulation time.
S10
Figure S7 The curvature of αβ-tubulin heterodimer represented by H7 orientation of the
unliganded heterodimer at (A) 300 K, (B) 277 K and of (C) the liganded heterodimer at 300 K
from the 2nd round simulations. The angles indicate the average deviation of heterodimers
shifting from the curved conformation in the crystal structure. The inset scheme at (C) describes
the structure caused by VLB with more bending than the crystal structure.
S11
Figure S8 The distance between charged residues contributing to the electrostatic surface. Each
panel is a comparison of a pair of charged residues under two different conditions. The dashed
line indicates convergence point.
S12
S13
S14
Figure S9 Helicity plots of H3, the new helix formed at T7 loop, H10 and H11 in α-tubulin
comparing the unliganded and liganded system at 300 K. The left is from the first round
simulations and the right is from the second round simulations. (same as below)
S15
Figure S10 Helicity plots of H5 in β-tubulin comparing the unliganded and liganded system at
300 K.
S16
Figure S11 Helicity plots of H3, the new helix formed at T7 loop and H10 in α-tubulin
comparing the unliganded system at 300 K and 277 K, respectively.
S17
Figure S12 Helicity plots of H3 and H7 in β-tubulin comparing the unliganded system at 300 K
and 277 K, respectively.
S18