In an absolute calculation the binding free energy of a ligand is calculated by completely removing the ligand from the protein-ligand complex. Alternatively one can perform relative calculations which compare the binding free energy between two ligands. During a relative calculation one ligand is transformed, via unphysical "alchemical" intermediate states, into another. The two ligands studied generally have a highly conserved chemical structure; this is both a strength and a weakness of the method, since the practitioner is restricted to study cogeneric ligands but benefits from potential gains in accuracy and precision resulting from studying smaller alchemical changes when compared to absolute methods. Cogeneric ligands also come with some other tangential benefits such as avoiding complicating factors such as standard states corrections . In this study, we have employed the ensemble simulation based TIES to correctly handle the uncertainties associated with such calculations and extended this to apply to free energy perturbation methods.