Relative binding free energy (RBFE) calculations have started to be used seriously in pharmaceutical companies in the last few years . A substantial limitation of RBFE is that it requires the compounds to be structurally and chemically similar to each other, confining its application to lead optimisation. To overcome this limitation, other approaches have been proposed for hit-to-lead discovery, including absolute binding free energy (ABFE) methods. These include approximate methods such as MMPBSA which are faster and less expensive. We have developed an approximate absolute binding affinity prediction method called "ESMACS" that ensures reliable and reproducible free energy predictions and is in use by some pharmaceutical companies . Given the approximations involved, it provides good and reliable ranking of ligand potency which is the most important thing desired during the initial stages of drug discovery. As leads start to emerge, more accurate ABFE predictions become necessary.