Binding Free Energy Predictions by NES



Predicted ΔG vs. Experiment


Correlations Between Experimental ΔG and Predicted ΔG

Metric Value [5%,95%]a StdErra p-value Pearson's r² 0.851 [0.416, 0.995] 0.178 8.795e-03 Kendall's τ 0.733 [0.077, 1.000] 0.306 5.556e-02 MAEb 0.425 [0.242, 0.633] 0.117 n/a RMAEc 0.387 [0.204, 0.952] 0.259 n/a

a 5% to 95% Confidence Intervals and Standard Error estimated using bootstrapping (1000 samples). bMean Absolute Error in kcal/mol. cMAE divided by the Mean Absolute Deviation of Experimental ΔG.



Robust Linear (RL) Modela of Experimental ΔG

Metric Value Slope 1.066 Intercept 0.571 MAEb 0.409 Relative MAEc 0.372

aA Huber estimator using the experimental data provided. bMean Absolute Error in kcal/mol. cMAE divided by the Absolute Average Deviation of Experimental ΔG.



Binding ΔG: Predicted and Experimental

Ligand Name Direct Preda,b RL Model Predd Experimenta ejm_46 -10.7 ± 0.1 -10.8 ± 0.1 -11.4 ejm_31 -10.5 ± 0.1 -10.6 ± 0.1 -9.6 ejm_54 -10.4 ± 0.1 -10.5 ± 0.1 -10.6 ejm_42 -9.7 ± 0.1 -9.8 ± 0.1 -9.9 ejm_43 -8.8 ± 0.1 -8.8 ± 0.1 -8.3 ejm_44 -7.3 ± 0.1 -7.3 ± 0.1 -7.5

aMaximum Likelihood Estimation using MBAR; Offset using the mean of the experimental data as a reference. bValues in kcal/mol. cNo experimental data provided. dA Huber estimator using the experimental data provided.



Predicted ΔΔG vs. Experiment


Correlations Between Experimental ΔΔG and Predicted ΔΔG

Metric Value [5%,95%]a StdErra p-value Pearson's r² 0.763 [0.582, 0.869] 0.089 4.873e-07 Kendall's τ 0.653 [0.448, 0.807] 0.114 1.715e-05 MAEb 0.836 [0.690, 0.974] 0.089 n/a RMAEc 0.551 [0.403, 0.825] 0.132 n/a

a 5% to 95% Confidence Intervals and Standard Error estimated using bootstrapping (1000 samples). bMean Absolute Error in kcal/mol. cMAE divided by the Mean Absolute Deviation of Experimental ΔΔG.



Robust Linear (RL) Modela of Experimental ΔΔG

Metric Value Slope 0.864 Intercept 0.000 MAEb 0.812 Relative MAEc 0.535

aA Huber estimator using the experimental data provided. bMean Absolute Error in kcal/mol. cMAE divided by the Absolute Average Deviation of Experimental ΔΔG.



Binding ΔΔG: Predicted and Experimental

RBFE Edge Direct Preda RL Model Predb Experimenta ejm_44_to_ejm_46 -3.3 ± 0.1 -2.9 ± 0.1 -3.9 ejm_44_to_ejm_42 -2.3 ± 0.1 -2.0 ± 0.1 -2.4 ejm_31_to_ejm_46 -0.6 ± 0.1 -0.5 ± 0.1 -1.8 ejm_46_to_ejm_54 -0.2 ± 0.2 -0.2 ± 0.2 0.8 ejm_42_to_ejm_54 -0.2 ± 0.2 -0.2 ± 0.2 -0.8 ejm_31_to_ejm_54 0.3 ± 0.1 0.3 ± 0.1 -1.0 ejm_31_to_ejm_42 1.1 ± 0.4 0.9 ± 0.4 -0.2 ejm_43_to_ejm_44 1.5 ± 0.2 1.3 ± 0.2 0.8 ejm_31_to_ejm_43 1.7 ± 0.1 1.5 ± 0.1 1.3 ejm_31_to_ejm_44 3.4 ± 0.2 2.9 ± 0.2 2.1

aValues in kcal/mol. bA Huber estimator using the experimental data provided. cNo experimental data provided.