For both systems we performed regression analysis using the W50 χ2 angle as the target variable (which clearly separates the "A" and "C" states, see Figure ). To help focus the regression analysis on the population shift of interest (away from the "A" state and towards the "C" state), we filtered frames to only include those with W50 χ1 angles ≥160° and ≤240°, effectively removing some "outlier" frames or those in the "B" conformational state, as described in the Methodology section. This left us with 9,281 and 9,714 frames (from the initial 10,000 each) for R1 and R4 respectively, with which to build our models, see Table for the relative populations of each state. obtained by performing regression analysis on the W50 χ2 angle, and using the mutual information (MI) as the metric. Positive scores depict an increased (relative) importance in the R4 variant, whilst negative scores depict an increased (relative) importance in the R1 variant. (C) Illustration of how the I7D mutation enhances the favorability of the "C" conformational state by enabling E101 to engage W50. (D) The interaction network surrounding N224D in R1. Interactions notably coupled to W50's conformation (see Table ) are indicated with black dashes indicating interactions which when strengthened favor the "A" conformational state, with red dashes favoring the "C" conformational state. (E) Projection of the per feature scores determined for the regression analysis (on the W50 χ2 angle using the MI as the metric) onto the structures of R1 and R4, focusing on features/interactions near the K146E mutation site. The thickness of the cylinder indicates the relative score of the feature/interaction. Cylinders are colored according to their interaction type, with red indicating a hydrogen bond, blue indicating a salt bridge, green indicating a hydrophobic interaction and purple indicating a van der Waals interaction.