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Figure 6
The W1 position is coupled to Asn254 conformations. (a) Radial (r, θ) plot for the QM/MM-MD simulation with Asn254 in the major conformation. The distance AZAC5–W1O is shown along r with the AZAC4–AZAC5–W1O–W1midpoint(H1,H2) torsion angle as θ. The red circle indicates values for these parameters derived from the crystal structure. W1 is relatively stable during the simulation at values close to experimental ones. (b) Following (a), but for the QM/MM-MD simulation with Asn254 in the minor conformation. In contrast to what is shown in (a), when Asn254 is in the minor conformation W1 moves to greater distances from C5 (maximum at 4.2 Å) exhibiting a broader distribution of different (225–255°) dihedral angles. (c)–(h) Cartoon snapshots from the simulations. (c)–(e) are from the simulation starting with the Pro253–Lys255 region in the major crystallographic conformation; (f)–(h) are from the simulation starting with the Pro253–Lys255 region in the minor crystallographic conformation. Thr57*, Asn254, W1 and 8AZA are in stick form with the protein backbone shown as a tube. Other water molecules are shown as lines. Broken cyan lines indicate hydrogen bonds. The minor Asn254 conformation facilitates W1 removal from the peroxo hole by stabilizing it in a new position toward the solvent-exposed of the active site at longer distance from C5. Supplementary Movies S1 and S2 are provided for the QM/MM-MD simulations.

IUCrJ
Volume 8| Part 1| January 2021| Pages 46-59
ISSN: 2052-2525
https://doi.org/10.1107/S2052252520013615