The predicted binding free energies from the 1-trajectory approach exhibit a high correlation with the experimental data (Figure ), with a Pearson correlation coefficient of 0.84. In a pharmaceutical drug development project, compounds are designed or selected for the same protein target. The ranking of the binding affinities is not affected by the energy of the protein Gpro (Eq. 1) when the conformational space is sufficiently sampled. Free energies of a protein differ in its bound and unbound states. The difference, called the adaptation free energy , provides an indication of the conformational changes of the protein and the energetic costs upon binding. Inclusion of adaptation free energies improves the correlations between simulations and experimental measurements in some cases , and does not have obvious effects in other cases . For the current data set of compounds, the binding site is relatively large. No significant strain is induced within protein upon compound binding. The inclusion of adaptation free energies of the protein degrades the correlations, with a correlation coefficient of 0.70.