The statistical models also revealed that positioning of the (natively) aromatic residues 66 and 100 affected selectivity in the radical cyclization. The positive coefficients associated with features describing residue 100 flexibility communicated that rigidity of this residue lead to greater enantioselectivity, while the negative coefficient associated with residue 66 in the aMD model (Residue 66Sterimol L) indicated that dynamic behavior of this residue facilitated selective transformations. To gain a deeper understanding of these effects, we interrogated the aMD conformational ensembles, which implied that W100 was involved in a network of competitive non-covalent interactions (NCIs) with flanking residues 66 and 177. Our analysis led us to postulate that when W100 preferentially interacts with residue 177, engagement with residue 66 is precluded. This results in increased mobility of residue 66, which allows residue repositioning and substrate binding. In concordance, IFD revealed significant repositioning of residue 66 upon substrate 6a binding (relative to apo, Fig. ).