Thermodynamic Integration with Enhanced Sampling (TIES), a new method to rapidly predict the ligand-protein relative binding affinities accurately, precisely and reliably, has been recently published by our group (http://pubs.acs.org/doi/abs/10.1021/acs.jctc.6b00979). It is based on the theory of thermodynamic integration (TI), a computational technique to calculate relative binding affinity through an alchemical transformation route. TIES allows one to rank a given set of congeneric drugs based on their strength of binding with a target protein. The most important and unprecedented feature of TIES is that the results yielded are reproducible. In our published work, we have applied TIES on a large set of alchemical transformations between ligands binding to a diverse set of target proteins and achieved excellent agreement between TIES predictions and the corresponding experimental values. We have also exhibited our capability to capture important chemical interactions of the biomolecular systems studied using TIES. One example is the entry of water molecules in the S1 pocket of thrombin when chlorine alchemically changes to hydrogen (see the figure below where red frames denote the probability of presence of water molecules). Due to all these unprecedented features, TIES has the potential to positively impact the drug discovery process saving both time and costs during its lead optimisation step.