# Introduction to protein ligand free energy calculations (FEP and FEP+)

**URL:** <https://gromacs.bioexcel.eu/t/introduction-to-protein-ligand-free-energy-calculations-fep-and-fep/8206>\
**Category:** User discussions\
**Created:** [February 2, 2024, 2:34pm UTC](https://gromacs.bioexcel.eu/t/introduction-to-protein-ligand-free-energy-calculations-fep-and-fep/8206 "2024-02-02T14:34:55Z")\
**Posts on this page:** 2\
**Page:** 1

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**Author:** ![ptrujillo](https://avatars.discourse-cdn.com/v4/letter/p/a9adbd/32.png) [@ptrujillo](https://gromacs.bioexcel.eu/u/ptrujillo)\
**Post date:** [February 2, 2024, 2:34pm UTC](https://gromacs.bioexcel.eu/t/introduction-to-protein-ligand-free-energy-calculations-fep-and-fep/8206/1 "2024-02-02T14:34:55Z")

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Dear, a pleasure to greet you. I am starting to calculate protein-ligand free energy. I have been reviewing many papers, but I can’t find a tutorial or protocol that I can follow step by step and adapt it to my system to do FEP or FEP+ in GROMACS, please, if you can guide me, I thank you very much,

stay tuned,

greetings,

Pablo

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**Author:** ![MagnusL](https://dub1.discourse-cdn.com/flex017/user_avatar/gromacs.bioexcel.eu/magnusl/32/2380_2.png) [@MagnusL](https://gromacs.bioexcel.eu/u/MagnusL)\
**Post date:** [February 2, 2024, 2:48pm UTC](https://gromacs.bioexcel.eu/t/introduction-to-protein-ligand-free-energy-calculations-fep-and-fep/8206/2 "2024-02-02T14:48:12Z")

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Welcome to the forum. Firstly, do you want to calculate absolute or relative binding free energies?

I don’t know of any step-by-step binding free energy tutorials. If you are interested in absolute binding free energy calculations, good starting points would be [Free energy of solvation — GROMACS tutorials https://tutorials.gromacs.org documentation](https://tutorials.gromacs.org/free-energy-of-solvation.html) and [Free Energy Calculations](http://www.mdtutorials.com/gmx/free_energy/index.html). [pmx](http://pmx.mpibpc.mpg.de/tutorial.html) is, as far as I know, more focused on relative binding free energy applications, but can almost certainly be of interest. Also, if you have not yet read [AlchemistryWiki](http://alchemistry.org/wiki/Main_Page), that might also be useful.