The Parsley force field provides competitive accuracy in relative binding free energy calculations for 199 ligands across eight different protein targets, as shown in Figure . Indeed, the differences in accuracy across the four force fields examined here are within 95% confidence intervals. It is also important to note that the accuracy of these calculations is strong affected by additional factors, including input structure preparation and sampling time. That said, in terms of mean unsigned error (MUE) of all relative free energy differences ΔΔ , Parsley (MUE = 1.02 kcal mol -1 ) ranks third, after GAFFv2.1 (MUE = 0.92 kcal mol -1 ) and OPLS3e (MUE = 0.93 kcal mol -1 ), and before CGenFF (MUE = 1.09 kcal mol -1 ). These results indicate that Parsley is a reasonable choice of force field for binding free energy calculations in drug discovery projects.