Figure 4.
Predicted binding affinities of fasudil analogues with α-synuclein from simulation are in line with subsequently measured chemical shift perturbation titrations from NMR. (A) Structures of fasudil and tested analogues, with ligand 47 having the highest affinity for α-synuclein and ligand 23 the lowest. (B) NMR chemical shift titration curves of the aromatic residues of the C-terminal region of α-synuclein with the five ligands depicted in panel A. (C) Slope of titration curves for each tyrosine residue in α-synuclein, and the average of all tyrosine residues in the C-terminal region of α-synuclein (Y125, Y133, Y136). (D) Titration curves of each compound for Y39, and for the average of all tyrosine residues in the C-terminal region of α-synuclein. Individual titration curves for Y125, Y133, and Y136 are shown in Figure S10. The CSP errors are based on the resolution of the spectra.
