Figure 14.

Results of protein–ligand binding free energy benchmarks. Each box represents the distribution across the individual RMSE (left) and Kendall’s τ (right) values of the different protein–ligand systems. In total, the results for each force field summarize binding free energies for 599 ligands in 22 congeneric series binding to 20 different protein targets. The metrics are based on the binding free energies ΔG calculated from relative ΔΔG values (1133 values for each force field) with Arsenic (now called Cinnabar).¹⁰⁴ The presented force fields are Parsley 1.0.0, Sage 2.0.0, GAFF2.1x/AM1-BCC, and OPLS3e (specific versions of GAFF2.1x given in SI for each system).