them, the Martini force field parameter for CER, CHOL and FFA were obtained from Marrink's study. (see Figure S4 and Table S1). Figure S4. CG models of CER ...
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Supplementary Materials: Influence of Temperature on Transdermal Penetration Enhancing Mechanism of Borneol: A Multi-Scale Study Qianqian Yin, Ran Wang, Shufang Yang, Zhimin Wu, Shujuan Guo, Xingxing Dai, Yanjiang Qiao and Xinyuan Shi 1. Interaction of Different Concentrations of BO with SC Lipid Membrane
Figure S1. The morphology evolution of lipid bilayer systems with different concentrations of BO added during the simulation time.
2. Interaction of Different Concentrations of OST with SC Lipid Membrane
Figure S2. The morphology evolution of lipid bilayer systems with different concentrations of OST added during the simulation time.
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3. Interaction of Different Concentrations of BO and 10%OST with SC Lipid Membrane
Figure S3. The morphology evolution of lipid bilayer systems with different concentrations of BO and 10% OST added during the simulation time.
4. Parameterization and Optimization of the CG Model In this project, the main molecules involved in our simulation systems are ceramides NS 24:0 (CER NS), cholesterol (CHOL), free fatty acids 24:0 (FFA), borneol (BO) and osthole (OST). Among them, the Martini force field parameter for CER, CHOL and FFA were obtained from Marrink’s study (see Figure S4 and Table S1).
Figure S4. CG models of CER NS, CHOL, FFA.
Figure S5. CG models of BO and OST.
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Table S1. Force field parameters of CER NS, CHOL, FFA. CER Atoms # 1 2 3 4 5 6 7 8 9 10 11 12 Bonds ij 12 13 34 45 56 27 78 89 9 10 10 11 11 12 Angles ijk 721 134 345 456 278 789 8 9 10 9 10 11 10 11 12
Name
Type
AM1 AM2 D1A C2A C3A C4A C1B C2B C3B C4B C5B C6B
P4 P5 C3 C1 C1 C1 C1 C1 C1 C1 C1 C1
Length (nm)
Kbond (kJ·mol−1·nm−2)
0.27 0.29 0.47 0.47 0.47 0.37 0.47 0.47 0.47 0.47 0.47
20,000 20,000 1250 1250 1250 20,000 1250 1250 1250 1250 1250
Angle (deg)
Kangle (kJ·mol−1·nm−2)
129 180 180 180 180 180 180 180 180
200 25 25 25 25 25 25 25 25 CHOL
Atoms # 1 2 3 4 5 6 7 8
Name
Type
ROH R1 R2 R3 R4 R5 C1 C2
SP1 SC1 SC3 SC1 SC1 SC1 SC1 C1
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Table S1. Cont. CHOL Bonds ij 12 23 24 46 47 56 67 78 13 14 34 35 45 57 Angles ijk 478 Impropers ijkl 1354 1357 1453 3574 4753 2134 2431 6457 6754
Length (nm)
Kbond (kJ·mol−1·nm−2)
0.242 0.260 0.341 0.213 0.544 0.203 0.368 0.425 0.493 0.604 0.272 0.346 0.294 0.406
20,000 20,000 20,000 20,000 20,000 20,000 20,000 1250 constraint constraint constraint constraint constraint constraint
Angle (deg)
Kangle (kJ·mol−1·nm−2)
180.0
25
Angle (deg)
Kimpropers (kJ·mol−1·rad−2)
0 0 0 0 0 −45 45 −45 45
100 100 100 100 100 300 300 300 300 FFA
Atoms # 1 2 3 4 5 6 7 Bonds ij 12 23 34 45 56 67 Angles ijk 123 234 345 456 567
Name
Type
FAC C1 C2 C3 C4 C5 C6
P3 C1 C1 C1 C1 C1 C1
Length (nm)
Kbond (kJ·mol−1·nm−2)
0.370 0.470 0.470 0.470 0.470 0.470
20,000 1250 1250 1250 1250 1250
Angle (deg)
Kangle (kJ·mol−1·nm−2)
180.0 180 180 180 180
25 25 25 25 25
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Because no Martini force field parameter for BO and OST had been reported before, we parameterized it using method provided in Martini website. Their chemical structures and CG mappings are shown in Figure S5 and their force field parameters are shown in Table S2. Table S2. Force field parameters of BO and OST. BO Atoms # 1 2 3 4 5 Bonds ij 12 14 23 25 34 45 24 Angles ijk 123 125 143 145 345 325 452 Dihedrals ijkl 5241 5423 3421
Name
Type
BOH BC1 BC2 BC3 BC4
SP1 SC1 SC1 SC1 SC1
Length (nm)
Kbond (kJ·mol−1·nm−2)
0.38 0.38 0.38 0.38 0.38 0.38 0.41
20,000 20,000 20,000 20,000 20,000 20,000 constraints
Angle (deg)
Kangle (kJ·mol−1·nm−2)
93.375 93.375 93.375 93.375 93.369 93.369 65.684
25 25 25 25 25 25 25
Angle (deg)
Kdihedral (kJ·mol−1·rad−2)
120 120 120
100 300 100 OST
Atoms # 1 2 3 4 5 6 7
Name
Type
OS1 OS2 OS3 OS4 OS5 OS6 OS7
SNa SC4 SC4 SC4 SN0 SC3 C3
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Table S2. Cont. OST Bonds ij 45 36 67 12 13 23 24 34 Angles ijk 245 345 136 236 436 367 Dihedrals ijkl 1243 5234 6243
Length (nm)
Kbond (kJ·mol−1·nm−2)
0.43 0.43 0.43 0.27 0.27 0.27 0.27 0.27
1250 1250 5000 constraints constraints constraints constraints constraints
Angle (deg)
Kangle (kJ·mol−1)
162.20 102.62 120.64 162.90 116.48 115.86
25.0 25.0 25.0 25.0 25.0 45.0
Angle (deg)
Kdihedral (kJ·mol−1·rad−2)
0.000 0.553 9.113
50 50 50
Then, in order to validate the accuracy of our model, we calculated the bond distributions of molecules in all atoms (AA) and CG levels. The results shown in Figures S6 and S7 indicated that all the bond distributions of BO and OST in CG representations were similar to those in the AA representations, which demonstrated that our CG models are valid for further simulation studies.
Figure S6. Bond distributions of BO molecules calculated from AA and CG simulations.
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Figure S7. Bond distributions of OST molecules calculated from AA and CG simulations.
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