Authors: Eric Wang & Jeff Klauda

Please email me at jbklauda@umd.edu if something isn't clear

Mutating a lipid means changing its chemical structure. We do this when our membrane contains a lipid which is not available by default in the CHARMM force field, but the structure is similar to an existing lipid. To mutate a lipid, you'll need to create your membrane with the pre-mutated lipids using CHARMM-GUI first.

Once that is done, modify the relevant .str file to include your mutated lipid. See the following path on ZT1 for an example for mutating CER240 to CER6. For small mutations, the IC table isn't necessary.
/afs/shell.umd.edu/project/energybio/shared/jbklauda/scripts/mutate/toppar_all36_lipid_sphingo.str

This mutation involved adding a few hydroxyls. When you add new atoms, you need to decide what the partial charges will be. You also may need to add new parameters for dihedrals or angles at the end of the .str file. CHARMM will give you an error if these are missing.

Mutate the lipids using mutate.inp An example is in the path
/afs/shell.umd.edu/project/energybio/shared/jbklauda/scripts/mutate/mutate.inp
The lipid names and how the atoms are deleted/renamed will need to be changed depending on your lipid.
Execute mutate.inp in CHARMM
set chm = “~jbklauda/charmm/c43b1/exec/gnu/charmm”
$chm < mutate.inp > mutate.out

Note that you will need to use the *inp files in this directory to build the files needed to run the MD simulation. The current CHARMM-GUI files will not work.

Run step5_assembly.inp to create the step5 input files.

You need to edit the *restraint.namd.str file to add your new lipid/s. Copy and paste an if/endif block of a similar lipid and rename it as a new lipid. If you have a more complex lipid you might also need to edit the *restraint2.namd.str file, so discuss this with Dr. Klauda.

Then run step5_input.inp to create the namd input files. If you look in step5_assembly.pdb, your lipid should be renamed and its structure changed. Make sure there aren't any broken bonds.

Finally, you will need to go into the namd subdirectory and validate that the restraints subdirectory has files with your new lipids listed. Moreover, you will need to make edits to the step5_input.colvar.str file to include reading in the new restraint (.ref) files in ./restraints subdirectory and remove those that are no longer present in your model.