64
After the completion of equilibration, the production run of each
of the unbiased MD simulation should be started. Again, in a similar fashion, a binary input file will be created using the grompp
module and a suitable protocol file. The MD protocol is available
in the online version and presented in Fig. 12.
1. The terminal commands for the input files are:
gmx_d grompp -f md_umbrella.mdp -c npt1.gro -t
npt1.cpt -p topol.top -r npt1.gro -n
index.ndx -o umbrella1.tpr
...
gmx_d grompp -f md_umbrella.mdp -c npt50.
gro -t npt50.cpt -p topol.top -r npt50.gro -n
index.ndx -o umbrella20.tpr
This protocol will create input for a 10 ns simulation for each
window. For demonstration issues this duration is adequate but
in case more accurate energy results are needed and depending
on your system, longer simulations might be necessary. After
having created the .tpr files run the simulations using the following terminal commands:
gmx mdrun -deffnm umbrella0
...
gmx mdrun -deffnm umbrella50
The ΔG bind of CC and CAN to 2-HP-B-CD can be estimated by
the potential of mean force (PMF) plot which is extracted from the
umbrella sampling procedure. The PMF of each simulation window will be calculated and plotted against the reaction coordinate,
which, in this case, is the COM distance. Given that the PMF plot
converges to a constant value at long distances, the difference
between the highest and lowest energy values corresponds to the
ΔG bind between the studied drug molecule and 2-HP-B-CD. In
order to calculate the PMF for each simulation window, the
weighted histogram analysis method (WHAM) will be used, which
is implemented in the WHAM module of gromacs.
The input to WHAM module consists of two files, one containing
the binary input of each simulation window (*.tpr files) and the
other containing the forces that the external potential imposes
onto the drug molecule that is dragged outside the CD’s cavity
(*pullf.xvg files).
1. Create a new document in a text processor (e.g., press this on
your terminal: vi tpr-files.dat) and make a list with all the .tpr
files in ascending order:
3.5.2 Umbrella
Sampling Simulations
3.6 Analysis
3.6.1 Create Input
Sofia Kiriakidi and Thomas Mavromoustakos
After the completion of equilibration, the production run of each
of the unbiased MD simulation should be started. Again, in a similar fashion, a binary input file will be created using the grompp
module and a suitable protocol file. The MD protocol is available
in the online version and presented in Fig. 12.
1. The terminal commands for the input files are:
gmx_d grompp -f md_umbrella.mdp -c npt1.gro -t
npt1.cpt -p topol.top -r npt1.gro -n
index.ndx -o umbrella1.tpr
...
gmx_d grompp -f md_umbrella.mdp -c npt50.
gro -t npt50.cpt -p topol.top -r npt50.gro -n
index.ndx -o umbrella20.tpr
This protocol will create input for a 10 ns simulation for each
window. For demonstration issues this duration is adequate but
in case more accurate energy results are needed and depending
on your system, longer simulations might be necessary. After
having created the .tpr files run the simulations using the following terminal commands:
gmx mdrun -deffnm umbrella0
...
gmx mdrun -deffnm umbrella50
The ΔG bind of CC and CAN to 2-HP-B-CD can be estimated by
the potential of mean force (PMF) plot which is extracted from the
umbrella sampling procedure. The PMF of each simulation window will be calculated and plotted against the reaction coordinate,
which, in this case, is the COM distance. Given that the PMF plot
converges to a constant value at long distances, the difference
between the highest and lowest energy values corresponds to the
ΔG bind between the studied drug molecule and 2-HP-B-CD. In
order to calculate the PMF for each simulation window, the
weighted histogram analysis method (WHAM) will be used, which
is implemented in the WHAM module of gromacs.
The input to WHAM module consists of two files, one containing
the binary input of each simulation window (*.tpr files) and the
other containing the forces that the external potential imposes
onto the drug molecule that is dragged outside the CD’s cavity
(*pullf.xvg files).
1. Create a new document in a text processor (e.g., press this on
your terminal: vi tpr-files.dat) and make a list with all the .tpr
files in ascending order:
3.5.2 Umbrella
Sampling Simulations
3.6 Analysis
3.6.1 Create Input
Sofia Kiriakidi and Thomas Mavromoustakos