Ligand binding studies are among the most important applications of MD simulations since this computational technique can capture the conformational dynamics of both the ligand and the receptor. It is thus possible to obtain a relatively accurate description of their physicochemical interactions, and both kinetic and thermodynamic information about the binding process. These results can be obtained if sufficient computational resources are available. While several methods have been developed to reduce the computational costs of obtaining accurate kinetic or thermodynamic data, MD simulations remain hindered by the timescale for sampling the relevant regions of conformational space, to obtain reliable estimates of thermodynamic properties. Our results highlight the potential of multi-eGO both as a model to benchmark and develop in silico free energy calculation techniques and as an accurate and efficient framework for ligand binding studies, potentially extending the current capabilities, in terms of time and number of particles, of in silico molecular studies.