Free energy perturbation, basically, involves one protein target, with a hybridized ligand (merged from a pair of similar ligands of interests), then we calculate the energy difference when gradually turning off the interaction of the first ligand while turning on the interaction of the second.
There is a detailed workflow, based on NAMD tutorial "A Tutorial on Alchemical Free Energy Perturbation Calculations in NAMD:" from Alchemical tutorial from NAMD ; and the paper describing Feprepare web server J. Chem. Inf. Model. 2021, 61, 9, 4131–4138
My github notebook discussed NAMD-FEP
If you can't access to github, you could get a PDF tutorial here (right click and save it if you wish):
NAMD-FEP-tutorial_from_github_quantaosun.pdf
