Figure 7

The ion coordination sphere affects HuPrP(90–231) dynamics in MD simulations.

(a) Superimposition of average structures sampled in the 2His and 1His trajectories. Helical domains are represented in blue and red in 2His and 1His, respectively, the β₁ and β₂ sheets are in yellow, coils are represented in gray (2His) and orange (1His); the non-OR regions are depicted using a wider transparent ribbon. (b) Root Mean Square Fluctuation (RMSF) of residues for the 2His and 1His simulations. RMSF was calculated fitting the coordinates of the complete protein (2His: green dot-dashed line; 1His: blue dotted line) or restricted to the C-terminal domain (2His: black line; 1His: red dashed line). In both simulations the N-terminal domain is, as expected, much more flexible with the exception of residues 226–231; the 2His simulation apparently features greater fluctuations but the differences fade out when only the stable C terminal domain is considered. Notable exceptions are residues H140 and R151. (c) Residue-wise β-sheet content for the 2His and 1His simulation as a percentage of sampling (150.0 ns); the 1His simulation shows unstable β-sheet formation between residues 106–109 and 114–117 (also shown in the inset). (d) Comparison of the first centroid obtained by clustering the N-terminal domain Cα atoms in the 2His (left) and 1His (right) simulations; residues 106–109 and 114–117 are shown in ball and stick (backbone is shown in magenta as in Supplementary Fig 3a); copper binding residues H96, Q98 and H111 are shown as sticks and the copper ion as a dark green sphere (note that M109 belongs to both groups); a number of residues forming hydrogen bonds unique to one system are explicitly labeled to improve clarity.