Specifically, residues roughly one a-helical turn apart couple most strongly from a geometric perspective and are similarly coupled in TC5b and TC10b. In comparison, non-nearest-neighbor charge couplings are stronger in TC10b than TC5b and indicate a network of residues with significant couplings up to 8 residues apart in primary sequence. Although it is not apparent from geometric analysis, this network of interactions can help explain differences in stability of the two peptides. Thus, our study highlights the complementary benefit of charge coupling analysis to interpret protein structure-function relationships. Although fully first-principles molecular dynamics remains cost prohibitive for proteins of typical size, advances in modeling such as artificial neural network potentials, polarizable force fields, or fragment-based methods could be paired with judicious choice of snapshots with DFT to capture important aspects of charge coupling. This analysis is also expected to be useful in the systematic design of QM regions for multi-scale modeling of catalysis where strong QM coupling of residues to an enzyme active site motivate their treatment with QM. ASSOCIATED CONTENT Supporting Information. Protonation states of TC5b and TC10b residues; RMSD of implicit and explicitly solvated TC5b; RMSD of implicit and explicitly solvated TC10b; SQM charge and geometric coupling for residue 1 in TC5b vs TC10b; Secondary structure analysis of SQM MD trajectories; SQM charge and geometric coupling for residue 2 in TC5b vs TC10b; SQM charge and geometric coupling for residue 4 in TC5b vs TC10b; QM charge coupling for residue 2 in TC5b vs TC10b; QM charge coupling for residue 4 in TC5b vs TC10b; Trajectory-specific SQM charge and geometric coupling for res. 1 in TC10b; 2D KDEs of charges between correlated pairs from full SQM of TC10b (PDF) from the Burroughs Wellcome Fund, an AAAS Marion Milligan Mason Award, and an Alfred P. Sloan award in Chemistry, which supported this work.