Using tLEaP prior to gromacs

GROMACS version: 2020.1.1
GROMACS modification: Yes/No
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Hello all

Just a quick question for advice regarding the use of tLEaP prior to using gromacs as I’m getting confused (sorry if this has been asked elsewhere, couldn’t find an answer):

I’m planning on using tLEaP to assemble my enzyme-ligand topology and coordinate files before I use ParmEd to convert the prmtop and inpcrd files into .gro and .top files. What I’m unsure of is whether I’d still need to use pdb2gmx since tLEaP/ParmEd alone doesn’t give you all the necessary files (position restraint for example).

Would it be best to use tLEaP to handle my ligands with GAFF and use pdb2gmx to deal with the enzyme separately? I feel like using tLEaP to process the whole enzyme-ligand system is great for AMBER simulations but not the best way for GROMACS use essentially.

Thanks in advance

In principle, things should work just fine. If you plan on using position restraints, you can always add them manually - by analogy to how pdb2gmx creates them. There’s no extra magic involved in topology generation, so a .top and a .gro are all you need to run a simulation; moreover, there’s a good chance that your ligand won’t pass through pdb2gmx without engineering new RTP entries and adding parameters from GAFF.

Hi Milosz,

Yes that makes sense. I was considering whether position restraints are even necessary? I can see why restraining a protein/enzyme is useful but is it necessary to restrain a ligand and/or water?

Useful yes, necessary not. If I ever use them, it’s usually to preserve the structure of one part of a model while equilibrating other parts of it, especially if the model was built from several smaller ones or by homology. Even though restraining RMSD in Plumed is a good alternative these days, it still slows things down quite a bit compared to running them in pure Gromacs.