Protein w Solute: Molecule Preparation - mms-fcul/CpHMD-container GitHub Wiki
Having the basis for our protein+molecule system created in the previous step, we now need to build the external molecule, the PNW. Since we are using the GROMOS force field, parameters for this will be obtained from the ATB website.
For GROMOS, the standard procedure to obtain an itp and force field parameters for a molecule is to submit it to the automated topology builder website.
Using the inhibitor .pdb constructed in the previous step (PNW.pdb) we will submit this molecule to the ATB to obtain its parameters.
Tip
To save time, the user can instead search ATB for an already parameterized molecule. Avoiding the submission process
From the ATB website, you will have the opportunity to verify the molecule that was submitted and download:
- an optimized structure for our molecule (in unitedatom since we are using GROMOS)
- The molecule itp
- a G54a7.ff with the added parameters for the molecule.
Important
It is important to verify if ATB added new atom types to build the requested molecule. If it was done so the force field obtained from the app: pdb2cphmd needs to be updated!
If the force field is not updated the simulation of the full step will for sure fail!!
It is imperative to ensure that the generated molecule is available for the CpHMD machinery to read it.
To do so, the molecule itp should be copied inside the force field folder in your running directory, which will be called in the simulation calculations.
Currently, the CpHMD code only supports three character residue naming <\ins><\b>, therefore it is required for the itp and residue naming to be changed accordingly.
In the case of this tutorial, ATB chose the name YG30, which was changed to PNW.
Proceeding with these changes, we added the molecule itp in the FF folder, and for the purpose of this tutorial the atom types of the molecule were all already in the provided force field.
With our external molecule already included in the force field, we are left with producing the parameters for the PB/MC calculation. Since the molecule can influence the protonation states of residues in our protein, we need to ensure that Delphi can take our new molecule into account.
To do so we need to update the Delphi databases with the radii and charges of the newly obtained molecule.
Firstly, the user needs to get the specific FF databases, which can be done using the extract app, resulting in a folder with the radii (.siz) and charge(.crg) databases:
singularity run --app extract-databases CpHMD.sif <force-field>
Secondly, the user must produce the new parameters for the molecule created. Charges are gathered from the .itp file of the molecule, while radii are created from Lennard-Jonnes rules with the parameters from the atom types in the ffnonbonded.itp present in the force field.
To get both parameters, we provide an app that can gather these from these files:
singularity run --app add-mol-db CpHMD.sif \
-f <force field name or custom path to ffnonbonded.itp> \
-i <molecule .itp>
-r <residue name to produce>
for our tutorial:
singularity run --app add-mol-db CpHMD.sif \
-f ./G54a7pH.ff/ffnonbonded.itp \
-i ./G54a7pH.ff/PNW.itp \
-r PNW
This app will produce a radii/charges-to-add-on-database.siz/crg containing the parameters for the PNW. In case the new molecule is not already contained within the database files, these two files must be merged with each database, respectively. For the case of PNW, this molecule is already in the standard database, therefore, merging the files is not required.
