Relative binding free Energy calculations in GROMACS between dissimilar molecules using bidirectional nonequilibrium dual topology schemes

We describe a step-by-step protocol for the computation of relative
dissociation free energies with GROMACS, based on a novel bidirectional
nonequilibrium alchemical approach.  The proposed methodology does not
require any intervention in the code. It allows computing with good
accuracy the RBFE between small molecules with arbitrary differences
in volume, charge, and Tanimoto index.  The procedure is illustrated
for the challenging SAMPL9 batch