We focus first on the effect of changing the N-terminal residue from Asn in TC5b (PDB ID: 1L2Y) to Asp in TC10b (PDB ID: 2JOF). The change in steric bulk between the two residues is limited, but the change in charge of the residue can be expected to alter which non-covalent interactions are preferred (Figure ). To carry out this analysis, we obtained geometric and charge correlations using DFT from 400 equally spaced snapshots obtained with SQM on 20 different trajectories each initialized from the NMR ensemble of the two structures (see Methods). Trends are qualitatively unchanged for both Ca coupling and for charges when considering the full SQM trajectory (Supporting Information Figure ). Most trends in geometric correlations between the first residue and the rest of the protein are unchanged with the Asn to Asp mutation from TC5b to TC10b (Figure ). In both proteins, the strongest positive geometric correlations of the first residue are to its nearest-neighbor residue (i.e., Leu2 in TC5b and Ala2 in TC10b, Figure ). Other strong positive correlations are with the Gly11, Gly12, Pro13, and Ser14 sequence at the opposite end of the a-helix to the N-terminal residue (Figure ). Considering instead charge coupling, individual trajectories have more distinct behavior between the TC5b and TC10b variants (Figure ). Here, a negative correlation indicates significant charge transfer between two residues. We note that very strong negative correlations are observed between Asp1 and Ala4, Lys8, or Ser20 in TC10b that are absent from interactions between Asn1 and the same residues in TC5b (Figure ). The observation of strong coupling between Asp1 and Ala4 is consistent with the design intent and with classical MD simulations[119] that indicated increased helical propensity was the source of higher stability for TC10b. This difference in helical propensity is also apparent in the SQM MD simulations, with the first four residues of TC10b having a higher fraction of snapshots assigned as helical in comparison to those of TC5b. (Supporting Information Figure ). These trends observed on the QM snapshots are consistent with those observed from SQM charges on the full 20 ps trajectories (Supporting Information Figure ). If we make comparisons of changes in coupling of the other two differing residues (i.e., Leu2 to Ala2 or Ile4 to Ala4 in Tc5b and Tc10b, respectively), both charge and geometric coupling appear more comparable between the two proteins (Supporting Information Figures ). The largest enhancements in coupling for Ala2 over Leu2 are with its nearest neighbor Asp1, although the geometric coupling for this same pair of residues is actually reduced in TC10b (Supporting Information Figure ). For Ala4 mutation from Ile4, enhanced charge coupling in TC10b is observed in individual trajectories with Asp1 or Lys8 (Supporting Information Figure ). Each of these residues has its strongest geometric couplings with its nearest neighbors in both protein variants, with only modest long-range coupling to more distant residues (Supporting Information Figures ). Observations are similar whether this analysis is carried out using SQM or QM charges (Supporting Information Figures ). Thus, from a geometric or charge coupling perspective, the main impact of mutations between TC5b and TC10b appears to be primarily due to changes in the electronic structure of the N-terminal Asn to Asp.