Extended Data Fig. 4: Simulations of dynamics, Asp162 conformations, and active-site pocket volume of Des27 and Des27.7.
From: Complete computational design of high-efficiency Kemp elimination enzymes
a. Joint distribution of the Asp162 conformational space in the unbound state. Conformation sampled by the χ1 and χ2 dihedral angles of the Asp162 side chain along MD simulations of the Des27 and Des27.7. In Des27 there are three distinct metastable Asp162 conformations, which are illustrated in the right panel. The conformation numbers labeled on the plots correspond to the stick representations on the right, with 5-nitrobenzisoxazole depicted in white sticks for reference. b-c. Visual representation of the calculated active site pockets in b. Des27 and c. Des27.7, using MDPocket isosurfaces. Yellow spheres represent the pocket volume. Asp162 is shown in sticks. Des27.7 exhibits an active site pocket that can better accommodate 5-nitrobenzisoxazole. d-e. Root mean square deviations (rmsd, Å) of the Cα-atoms from MD simulations. Data was collected every 400 ps from 5 replicas of 1 µs length each. The gray lines show the five individual runs, and the colored solid line shows a rolling average of the rmsd from all five replicas for each system. d. rmsd for unbound systems Des27 (left), Des27.7 (right) e. rmsd for bound systems Des27 (left), Des27.7 (right).
