From our calculations, the G202R mutation does not appear to directly impact the conformational sampling of the W50 side chain, as no notable non-covalent interactions were identified that differ between the "A" and "C" conformational states for either the R1 or R4 variants (Figure ). Instead, this mutation has been shown by EVB calculations to provide transition state (TS) stabilization, which would not be detected by our approach (given both that these are classical MD simulations, and that the conformation of W50 is the target variable).