1. ZEPHYR + GROMACS José R. Valverde CNB/CSIC jrvalverde@cnb.csic.es
MD tutorial
ZEPHYR + GROMACS
José R. Valverde
CNB/CSIC
© José R. Valverde, 2014
CC-BY-NC-SA

2. Simulation in vacuo

3. Getting started
Open a terminal and type “zephyr &”

4. Zephyr main window
Zephyr offers a GUI to simplify running standard MD simulations using GROMACS.
You can select the starting configuration as a PDB file
By default it offers a tutorial example: alanylalanine
You can select the output directory
Results will be saved in a sub-directory of it
By default it offers “zephyr_sims” on your home.
Procceed to “Parameters”

6. MD parameters
Here you can select the parameters that will drive the MD simulation.
Whether a minimization should be done first
Length and time step.
Temperature (in various scales) and force field
Solvent viscosity and implicit water model (more or less accurate)
Sampling periodicity (how often to save configurations)
Uncheck VMD and proceed to “Simulation”

9. Create working directory
Your simulation will be saved on a specific subdirectory named after the starting PDB file.
It will be placed below the directory you originally selected, thus for our example
~/zephyr_sims/alanylalanine_capped
All resulting files will be found there

11. Simulation run
Zephyr now proceeds to invoke GROMACS to run the simulation
Depending on your choice of parameters it may run faster or slower. This one should go very fast!
IFF YOU HAVE VMD installed and configured, you can use it to monitor directly the progress of the simulation visually as it runs.

13. Wait... This can be the most tiresome part of the work.
You must wait for the computer to finish the calculations
Depending on your option choices and hardware, this may require up to several months of calculations!
So... you better get the simulation parameters right from start!

15. View the trajectory Inspect the trajectory using UCSF Chimera
Close Zephyr (close the window --“x”)
Open UCSF Chimera
Go to the Tools menu and select MD/Ensemble Analysis
A sub-menu pops up, choose “MD movie”

17. Opening a trajectory Now we need to open the trajectory data:
MD simulation parameters
TPR file
Time-step, simulation length, box size, conditions...
Sampled values
TRR file / XTC file
Coordinates, Energies, etc...
Select the newly generated TPR file
zephyr_sims/alanylalanine_capped/......tpr

19. Load the trajectory Open the corresponding TRR file
Make sure it matches the TPR file you selected earlier
In other words: the parameters and the trajectory must correspond to each other.

21. Play You can now view the progression of the simulation
Once or many times (loop)
At various speeds
Displaying only one every so frames
You can carry out and plot several analyses
You can even create a movie

23. Continuation run

24. Continuation runs Sometimes simulations are too short
You could not detect an interesting phenomenon
You could not run a longer simulation
The simulation was stopped by external forces...
You can use a previous run as the starting point and extend it for longer periods
Open Zephyr
Choose Trajectory File (.trr) from previous run
alanylalanine_capped_processed_box.em.md.trr

26. Choose parameters and length
If you did run your simulation with Zephyr, it is usually better to let Zephyr “Auto load mdp params”
If that fails or you used tailored parameters, you may need to click “Load mdp now” to choose them
Select the total time to simulate in the continuation run
Click on “Continue simulation”

28. Explicit solvent model

29. Explicit solvent The previous run used an implicit solvent model
I. e. water molecules were not actually there, but their effect was simulated by increased viscosity
We did not consider solvent electrostatic effects (e.g. water has a dielectric constant of 80)
We can ask Zephyr to make and solvate a box for us, filling it with explicit water molecules at random coordinates, and equilibrate charges with ions.
Click on “Use explicit solvent”

31. Reduce simulation time
Adding water will increase the number of atoms to model
Running time grows roughly with the square of the number of atoms
When using solvent, membrane, etc... we will need to adjust the simulation time
TIP: start with a short run to verify everything is OK and the continue it as needed
Select “100” steps.

33. Wait After clicking “Simulate” the process will be started
This time the system is considerably bigger
Steps will take longer
You may be able to see that there is a preparation, a minimization and the actual MD run.

35. Long running times
As you can see, when the model size grows, time also grows, and to a larger extent.
For complex models, it may require specialized hardware
GPUs (note that you can select it in the parameters window)
Clusters (in this case you will need to run the simulation manually)
In large cases you will likely fine-tune parameters and split the run in “pieces” or “sessions”

37. Visualize the system
This is a very short run, so we will not have a meaningful trajectory
But we can see what Zephyr did to our system:
Open UCSF Chimera
Open the Gromacs file used for the run
alanylalanine_capper_processed.box.wat.ion.em,gro
See how Zephyr/GROMACS created a box filled with water molecules and ions around the molecule.

39. Fine-tuning simulations

40. Fine tuning simulations
Open Zephyr once more
Proceed to parameters
Click on “Advanced Parameters”
Inspect the options.
Look at alternative nominal values
You can save the fine-tuned parameters to a file and use it later in subsequent simulations.
You can load a previous parameter file and use or modify it.

42. Going pro...
You can look at the saved parameter files with any text editor and hand-modify them
You can look at the coordinate files with any text editor and hand-modify them
Useful to adapt atom names to FF expectations
You can generate advanced models with other tools
Check out PACKMOL
Read GROMACS manuals and tutorial

43. That was all just the beginning folks!
Image by Web-Master. CC0.