Analysis of conformational changes predicted by MD simulations of the p.F381S CRBN construct. (A) Conformations of residues located in the surroundings of the p.F381S mutation are shown in the representative conformation from MD simulations of the mutant construct (C atoms in green) compared with the crystal structure of WT CRBN (C atoms in light blue). (B) A similar comparison focused on Len binding site shows smaller deviations mainly for residues exposed to the solvent (eg, H357, H397, W400). (C) Distribution of RMSD values calculated on MD simulations of the p.F381S construct for residues located in both binding site and mutation site (5 Å from Len and the mutated residue, respectively).