Although enhanced a-helical propensity in classical MD simulations of TC10b suggests that fixed-charge force fields are able to capture some degree of enhanced stabilization for the mutant[119], the variations in partial charges we observe on the residues as hydrogen bonds dynamically form and break cannot be captured by fixed-charge force fields. We next aimed to gain a global view of charge and structural differences between TC5b and TC10b by computing the linear correlations among QM charges and Ca motions for all residues in the two proteins over all 20 trajectories. Although it is known that TC10b has enhanced stability with respect to the TC5b protein, few variations in geometric coupling are apparent between the two proteins (Figure ). Furthermore, the areas of greatest change in structural correlations do not involve the N-terminus and instead correspond to differences in the anti-correlated motion of Ser13-Arg16 versus Asn5-Asp9 (Figure ). Furthermore, the strongest couplings are consistently nearest-neighbor interactions, with relatively few positively correlated interactions between Asp1/Asn1 and neighboring residues (Figure ). Variations in charge coupling are much more apparent between the two proteins (Figure ). Here, the more stable TC10b has enhanced negative correlations (i.e., charge-transfer-mediated couplings) between Asp1-Ala4 and neighboring residues 1-8 (Figure ). This enhanced charge coupling is likely a signature of stronger interactions in the a helix. The salt-bridge between Asp9 and Arg16 also has stronger coupling in the TC10b variant (Figure ). Thus, overall analysis of charge coupling suggests strengthened interactions in comparison to the TC5b variant for the first four residues of the protein both with each other and with more distant residues. While most charge correlations between Asp1 and surrounding residues are stronger in TC10b than those for Asn1 with surrounding TC5b residues, we note one exception. The Gln5 residue in TC5b appears to have a stronger correlation with Asn1 than Gln5 with Asp1 in TC10b (Figure ). To identify the structural significance of this variation, we examined the trajectories over which the Asp1-Gln5 or Asn1-Gln5 couplings were strongest (Figure ). We noted that in both of these cases, the coupling between the Asp1 terminal NH3 + and Ser20 terminal carboxylate is reduced compared to the average due to competing interactions, but the Asn1-Ser20 charge correlation is essentially absent in the case of TC5b (Figure ). In both cases, the N-terminus backbone forms a hydrogen bond with Gln5's carbonyl sidechain to orient Asp1 or Asn1 away from any other sidechains (Figure ). When Asp1 is more highly charged, this hydrogen bonding interaction is disrupted, in part because the Asp1 sidechain forms an intramolecular hydrogen bond with the terminal NH3 + (Figure ). This analysis suggests that the different hydrogen bonding capabilities of the Asn1 sidechain cause the residue to preferentially interact with Gln5 instead of with the C-terminus, potentially contributing to the lower stability of the TC5b variant. The cartoon structures are colored the same as the symbols in the graph that show the extreme values of charge (i.e., blue for positive Gln5 charge and orange for relatively negative Gln5 charge) for Asn1 or Asp1 with Gln5, and other atoms are colored as follows: nitrogen in dark blue, oxygen in red, and hydrogen in white.