Figure 2.

When in contact with α-synuclein, fasudil dynamically shuttled between different binding modes with different interactions; multiple specific interactions were rare in any given binding mode. (A) The probability of observing interactions between fasudil and α-syn-C-term categorized by type of interaction in the bound ensemble. We note that a given residue can only form certain types of interactions. Error bars were calculated by blocking (see SI for more details). (B) Conditional interaction probability of observing a specific interaction between α-synuclein and fasudil in the bound ensemble, given that a charge–charge interaction had formed between D135 and fasudil. (C) Illustration of the stacking orientation between fasudil’s isoquinoline ring and the Y133 side chain. R is the distance vector between the centers of mass of the six aromatic carbons of Y133 and ten aromatic atoms of the isoquinoline ring on fasudil. The distributions are normalized and shown on a logarithmic scale. (D) Time series of a representative portion of the unbiased MD trajectory of α-synuclein with fasudil showing the formation of different interactions. The presence of a line indicates the formation of a particular interaction. Trajectory frames were sampled every 180 ps.