Protein in Solution: CpHMD settings - mms-fcul/CpHMD-container GitHub Wiki
With a completely minimized and initialized system, we are now in a position to perform CpHMD simulations! It is advisable to use a separated folder for the CpHMD production to avoid unnecessary clutter.
For the sake of simplicity, in this tutorial we will use the most basic setup for CpHMD. Therefore in the CpHMD production folder you should have the CpHMD-basic.settings file present in the templates of this repository.
This is the major step in succeeding on running CpHMD. All the details and information of the simulation are contained within this single file that is treated by the program.
Tip
If you are interested in knowing more of all the possible flags of CpHMD, please visit its guide file in CpHMD settings
The sections that require your attention are divided in:
- simulation settings and files
- mdp section
The first section is where you define the general settings to run the production.
Only the lines that require caution will be highlighted in here, since the other lines have a small description in the file and are quite easy to understand.
Important
- sites="all 1N 129C" - defines the residues that are titrating. It is arguably one of the most important flags of the .settings file!
The site's definition will dictate which residues will be considered as titratable. Even if you changed them to the CpHMD compliant name, they may not be titrating if you don't include them in this list.
From this line, the CpHMD run will produce a .sites file with an indication of all titratable residues and their respective tautomers, so that the PB/MC cycle can define, at the simulation pH, which is the preferred state of each site.
Firstly, to construct this line, you need to define whether your termini are titrating. If they are uncapped they should always be titrating, hence they should be inserted into the sites as their residue number, followed by N and C for which termini it is.
Secondly, you should define the residues in your structure that should be titrating. This can be done either through a string of residue numbers or through the flag all.
Caution
The all flag will check your structure file for all residue names ending with a number (AS4, HI2, TY0 ...) and will consider them as titratable. It implies that only the CpHMD titratable amino acids end in a number due to their tautomers.
If, perchance, you have custom residues that end in a number, the all flag may raise problems.
Tip
To confirm that the sites line given by the user is correct, we provide a container app to write the .sites file as it will be used by CpHMD This can be done via the command:
singularity run --app make-sites CpHMD.sif <CpHMD.settings file>
The following settings define the location of your simulation files to run the production. These should be updated with the user-specific pathways to correctly reference the topology, gro, and index files. Considering the provided tutorial folder layout, they should be:
- TOPin="../boxmin/HEWL.top"
- GROin="../boxmin/init2.gro"
- NDXin="../boxmin/index.ndx"
- CpHcontainer="../boxmin/CpHMD.sif"
The following section is the definition of your .mdp file for the MD simulations. It is possible to note that every line of this section starts with "#mdp#", which is a section required flag for the program to identify the lines and create a .mdp file for production.
In this region, you should set all your system-specific parameters, which will not be discussed in this tutorial since they are within the scope of regular MD parameters.
Caution
Please remember that this section should be changed depending on the force field chosen and tailored to your needs.
The .settings file ends with the fixgro section, which contains the inputs for a tool created by António Baptista to correct PBC artifacts on multiple solute systems. One may note that this section is recognized by the workflow with the "#fixgro#" at the line start
Often, the structure files saved from the MD steps may contain PBC artifacts that separate solute molecules across the periodic images. This becomes a problem when entering the PB/MC cycle since PB calculations need a whole system without these artifacts.
Note
Since this tutorial is a single solute (our protein) we do not need to edit or even have the commands for the fixgro program.
