  The accurate prediction of protein-ligand binding affinities is crucial for
drug discovery. Alchemical free energy calculations have become a popular tool
for this purpose. However, the accuracy and reliability of these methods can
vary depending on the methodology. In this study, we evaluate the performance
of a relative binding free energy protocol based on the alchemical transfer
method (ATM), a novel approach based on a coordinate transformation that swaps
the positions of two ligands. The results show that ATM matches the performance
of more complex free energy perturbation (FEP) methods in terms of Pearson
correlation, but with marginally higher mean absolute errors. This study shows
that the ATM method is competitive compared to more traditional methods in
speed and accuracy and offers the advantage of being applicable with any
potential energy function.
