115
parmchk –i IRB.mol2 –f mol2 –o IRB.frcmod
Missing parameters are included in the IRB.frcmod output
file.
5. Assign force field and construct a parameter library for IRB
with the tLEaP module of AMBER. The general AMBER force
field (GAFF) was used to assign force field parameters to IRB
[19]:
(i) Open tLEaP program:
tleap
(ii) Load force field:
source leaprc.gaff
(iii) Load mol2 file for IRB:
MOL = loadmol2 IRB.mol2
(iv) Load missing parameter file for IRB:
loadamberparams IRB.frcmod
(v) Save library for IRB:
saveoff MOL IRB.lib
The generated output IRB.lib and the IRB.frcmod will be used
later for complex construction.
2-HP-β-CD preparation: RESP charges for all atoms of
2-HP-β-CD, missing parameters (2-HP-β-CD.frcmod), and
library files only for the 2-HP part of cyclodextrin (2-HP.lib) are
generated similarly as in steps 1–5 above during IRB preparation.
AMBER employs a well-tested force field for the treatment of sugars (i.e., cyclodextrin); however, modified structures cannot be
supported. Therefore, one may treat the 2-HP part of 2-HP-β-CD
as a small molecule with GAFF and has to manually generate a
library file (2-HP.lib) as commented above.
IRB:2-HP-β-CD complex preparation: Construct topology and
coordinate files, which will be used as inputs for MD simulations.
The force field GLYCAM 06 [20] is used to treat the CD part of
2-HP-β-CD while GAFF is used for the 2-HP part. The TIP3P
water model is employed for the treatment of solvation [21].
(i) Open tLEaP program:
tleap
(ii) Load force fields:
source leaprc.gaff
source leaprc.GLYCAM_06j-1
(iii) Assign explicit model for water molecules:
Molecular Dynamics and Drug Complexation with Cyclodextrins
parmchk –i IRB.mol2 –f mol2 –o IRB.frcmod
Missing parameters are included in the IRB.frcmod output
file.
5. Assign force field and construct a parameter library for IRB
with the tLEaP module of AMBER. The general AMBER force
field (GAFF) was used to assign force field parameters to IRB
[19]:
(i) Open tLEaP program:
tleap
(ii) Load force field:
source leaprc.gaff
(iii) Load mol2 file for IRB:
MOL = loadmol2 IRB.mol2
(iv) Load missing parameter file for IRB:
loadamberparams IRB.frcmod
(v) Save library for IRB:
saveoff MOL IRB.lib
The generated output IRB.lib and the IRB.frcmod will be used
later for complex construction.
2-HP-β-CD preparation: RESP charges for all atoms of
2-HP-β-CD, missing parameters (2-HP-β-CD.frcmod), and
library files only for the 2-HP part of cyclodextrin (2-HP.lib) are
generated similarly as in steps 1–5 above during IRB preparation.
AMBER employs a well-tested force field for the treatment of sugars (i.e., cyclodextrin); however, modified structures cannot be
supported. Therefore, one may treat the 2-HP part of 2-HP-β-CD
as a small molecule with GAFF and has to manually generate a
library file (2-HP.lib) as commented above.
IRB:2-HP-β-CD complex preparation: Construct topology and
coordinate files, which will be used as inputs for MD simulations.
The force field GLYCAM 06 [20] is used to treat the CD part of
2-HP-β-CD while GAFF is used for the 2-HP part. The TIP3P
water model is employed for the treatment of solvation [21].
(i) Open tLEaP program:
tleap
(ii) Load force fields:
source leaprc.gaff
source leaprc.GLYCAM_06j-1
(iii) Assign explicit model for water molecules:
Molecular Dynamics and Drug Complexation with Cyclodextrins