Fig. 4.

FMO results for the TAF1 in complex with 2, 4 and 5. A Extending the ligand leads to perturbance of water network and drop of affinity in 4. In 5, the water network is recovered, and affinity maintained. B Energetic contributions of individual water molecules to the stability of the overall water network. Change in the median FMO calculated ‘happiness’ of the water network follows the expected trend. C FMO-PIE generated contribution to ligand binding energy in kcal/mol per fragment residues. Red indicates favourable interaction energies, whereas green indicates unfavourable interaction energies. The sum of these interactions is shown in Table 1 as Ligand PIE