8.1. Frangment ER

Calculate relative binding free energy between protein and ligand using Fragment ER method.

Purchase of add-on is necessary for using.

We use NAMD for molecular dynamics solver.

8.1.1. Fragment ER window

File menu
New Project
Initialize the project.
Open Project
Open the project.
Save Project
Overwrite and save the project.
Save Project As
Save the project with a name.
Close
Close the Fragment ER window.
MD menu
NAMD Keywords Setup
Open NAMD Configure window.
Run NAMD
Run NAMD locally.
Run NAMD On Remote Server
Open Remote Job Submission window for NAMD execution on remote server.
Edit .log File
Open the log file at NAMD execution with a text editor.
Energy Plot
Draw graph of energy change from log file at NAMD execution.
Import NAMD Trajectory
Open the MD trajectory.
Clear NAMD Output Files
Delete the output file made by NAMD execution. Delete RunNAMD.bat, RunNAMD.log, various dcd, log, coor, namd, vel, xsc, xst files etc ..
Analysis menu
Calculate Free Energy
Calculate free energy.
Edit .log File
Open the log file at free energy calculation with a text editor.
Import Result
Import the free energy calculation result and display it in Result display window.
Clear Analysis Output Files
Delete the output file made by free energy calculation. Delete FreeEnergy.sh, FreeEnergy.log, calc_PdP_kai2.out, parameters_fe file, refs, soln folder etc.
Tools menu
Preferences
Preferences window is displayed.
Solution
Specify PDB file of solution type by clicking button. If more than one ligand molecule is present, designate the ligand molecule. Ligand molecules are displayed in the view.
Set Core
By clicking on the atom of the fragment part from the initial ligand and clicking the Set Core button, the remaining part is set as the mother nucleus.
Add
After selecting a new fragment with a combo box, click the Add button to add the ligand with the new fragment added to the mother nucleus to the final ligand list.
Configure
Fragment ER setting window is displayed.
Check
It checks whether atom types of mother nuclear parts of various ligands match. At the same time it generates force field of ligand.
Setup
Generate input file (PDB, PSF file) of NAMD.
Close
Close the Fragment ER window.

8.1.2. Fragment ER setting window

Set up Fragment ER calculation. The setting contents are recorded in the project file.
Solvation
Drop water and solvate for In-protein
Set whether water molecules should be rearranged by calculation of In-protein system. If you do not do this, water molecules of the solution system you read will be used as a solvent. If this is not done, periodic boundary cells must be set.
Drop water and solvate for In-aqua
Set whether water molecules are rearranged by calculation of In-aqua system. If you do not do this, water molecules of the solution system you read will be used as a solvent. If this is not done, periodic boundary cells must be set.
Distance from solute to cell boundary
Specify the distance from the solute to the periodic border cell.
Forcefield for Ligands
Select the type of force field to use for the ligand.
N-terminal modification
Specify N-terminal modification of protein.
C-terminal modification
Specify the C-terminal modification of the protein.
Import trajectory Interval
Specify how often to thin out when trajectory is imported.
ERmod
# of bins for binding energy
Specify the division number of binding energy.
# of insersions for solute (maxins)
ermod Specify maxins at runtime.
# of division of the simulation (engdiv)
ermod Specify engdiv at run time.
# of OpenMP threads (for local run)
ermod Specifies the number of OpenMP threads on local execution.
# of MPI processes (for remote run)
ermod Specifies the number of MPI processes at remote execution.
OK
Save the settings and close the window.
Cancel
Close the window without saving the setting.

8.1.3. NAMD Configure window

Set up MD calculation by NAMD. The setting contents are recorded in the project file. Select the system to be calculated with the check box.
Conf

Set the input file for NAMD calculation of each system.

numdcd
Specify the output interval of the trajectory.
numlog
Specify the output interval of the log file.
temperature
Specify the temperature. In the equilibrium calculation of In-protein, it is the temperature at the first stage of the stage temperature rise.
timestep
Specify the time step of 1 step of MD.
numstep
Specify the number of MD steps.
Number of Therad
Specify the number of threads when NAMD is executed.
Generate Conf Files
Output the input file (namd file).
Run
Output the input file and execute NAMD locally.
Close
Close the NAMD Configure window.
Load Default
Load default setting condition.
Save Default
Save the current setting condition as the default setting.
Reset Default
The default setting condition is reset to the initial state.

8.1.4. Result display window

A summary of the results is displayed in Summary. A graph of the energy distribution function is displayed. You can select which system to display.
log
Open the log file with a text editor.
Excel
Save the data displayed in the graph as a CSV file and open it with the application.
Close
Close the result display window.

8.1.5. Preferences window

NAMD Path
Set the path of the NAMD executable file.
Protein Topology Path
Specify the protein topology file.
Protein parameter Path
Specify the protein parameter file.