Note that the pose with the most favorable (negative) binding free energy contributes the most to the overall binding free energy. The numerical uncertainty due to finite simulation time during the free energy runs was estimated by five-block blocking analysis for each pose and propagated through Eq 1 to obtain the uncertainty of the overall binding free energy, using the python package Uncertainties of Eric O. Lebigot. We report metrics of performance (e.g. area under the receiver operating characteristic curve) based on the more favorable overall binding free energy from the two independent runs for each ligand.