Supporting Information
Increasing the Sampling Efficiency of Protein Conformational
Transition Using Velocity-scaling Optimized Hybrid
Explicit/Implicit Solvent REMD Simulation
Yuqi Yu,1, § Jinan Wang,1, § Qiang Shao,1,* Jiye Shi,2,* Weiliang Zhu1,*
1
Drug Discovery and Design Center, ACS Key Laboratory of Receptor Research, Shanghai Institute of
Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China
2
§
UCB Pharma, 216 Bath Road, Slough SL1 4EN, United Kingdom
These authors contributed equally to the work.
*To whom correspondence should be addressed. Qiang Shao, Tel: +86 21 50806600-1304, E-mail:
qshao@mail.shcnc.ac.cn; Jiye Shi, Jiye.Shi@ucb.com; Weiliang Zhu, wlzhu@mail.shcnc.ac.cn.
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Figure S1. Root-mean-square deviation (RMSD) histories of single replicas in (a) hybrid and (b)
standard REMD simulations of the N-terminal domain of calmodulin. RMSD values were calculated for
backbone of four helices by fitting to the closed structure of NTD. (c) Superposition of the
representative structure with high RMSD values in (a) and (b) (cyan color) to the crystal open structure
(green color). (d) Superposition of the representative structure with low RMSD values in (a) and (b)
(pink color) to the crystal closed structure (red color).
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Figure S2. Root-mean-square deviation (RMSD) values of the N-terminal domain of calmodulin
collected at 300 K for (a) hybrid and (b) standard REMD simulations.
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Figure S3. Superposition of the representative structures corresponding to the local minima of ΔDrmsd ~
2.5 Å for hybrid REMD (gray color) and standard REMD (cyan color) with the crystal open structure
(green color) of NTD.
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Figure S4. Superposition of the representative structures corresponding to the local minimum of ΔDrmsd
~ -2.5 Å for hybrid REMD (gray color) and the local minimum of ΔDrmsd ~ -2.0 Å for standard REMD
(cyan color) with the crystal closed structure (red color) of NTD.
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Figure S5. Superposition of the representative structure of the transition state obtained from hybrid
REMD (gray color) with the crystal open structure (green color) and closed structure (red color).
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Figure S6. (a) time series of ⊿Drmsd in typical replicas of hybrid and standard REMD simulations and
three independent trajectories of conventional MD simulations. (b) The comparison among the finally
achieved structures from the conventional MD simulations (yellow color) as well as standard REMD
simulation (cyan color), and the crystal closed structure of NTD (red color).
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Figure S7. (a) Superposition of the representative structure of the upper region of the broad cluster (gray
color) corresponding to the closed state in Fig. 6 with the crystal closed (red color) and crystal open
(green color) structures of NTD. (b) Superposition of the representative structure of the lower region of
the broad cluster (cyan color) corresponding to the closed state in Fig. 6 with the crystal closed (red
color) and crystal open (green color) structures of NTD. The orientations of the four helices in the
crystal closed and open structures are shown by arrows.
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