This approach involves dividing an alchemical transformation into several steps with fixed values of the alchemical parameter, λ (referred to as λ-windows hereafter), and performing simulations at each λ-value such that the system always remains in equilibrium. We use thirtheen λ-windows for ligand (de)coupling both in water and protein environment with λ = {0.0, 0.01, 0.05, 0.1, 0.2,....,0.9, 1.0}.