Nowadays, binding free energy calculations are essential for the study of chemical and biological systems. However, accurate methodologies in the field are often computationally demanding, which limits their applicability. As an alternative, we introduced the Central Limit Free Energy Perturbation (CL-FEP) approach (1). Without computing intermediate points of a system transformation (e.g. stratified coupling and decoupling of a ligand), CL-FEP can deliver accurate free energy change values. In CL-FEP, the exponential average estimator is evaluated upon transforming the energy output of molecular dynamics simulations by applying the Central Limit theorem. Importantly, energies from explicit solvent simulations can be used to evaluate the estimator and no fitted parameters are introduced by our implementation.