How to set up protein–peptide complex simulation in GROMACS: peptide as ligand or whole complex?

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I am new to molecular dynamics simulations and I want to simulate a protein–peptide complex using GROMACS. Should I treat the peptide as a ligand and set it up separately, or should I consider the entire protein–peptide complex together as one system for the simulation? Which approach is recommended for this purpose?

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Hi,

In principle, my suggestion would be to stick closely to the “real” biological system. If you have a structure of the peptide–protein complex (e.g., a crystal structure), you should probably use this as the initial structure for your simulations. However, if the structure of the complex is unknown but the binding pocket is known, you could try modeling your peptide into the pocket or even attempt an unbiased binding simulation (computationally demanding!).

Regarding the organization of the simulation, I would recommend using separate .itp files for the protein and the peptide, as this makes it easier to keep an overview. You can perform all system preparation steps, including .itpgeneration, either with your local GROMACS installation or via the CHARMM-GUI web server.

Best,
Marius