Mulliken partial charges from GFN2-xTB were collected for 20 ps (i.e., 40,000 steps) for each of the 20 starting structures for both mutants. These charges were summed over each residue to mitigate shortcomings of the Mulliken partial charge scheme as in prior work . Both charges and structures were recorded at every timestep. A subset of 400 evenly-spaced structures (i.e., every 0.2 ps) from the SQM MD runs were used to collect density functional theory (DFT) partial charges with the long-range corrected, range-separated hybrid wPBEh functional (w = 0.2 bohr -1 )[134] and the cc-pVDZ[135] basis set using implicit C-PCM solvation. Charge covariance and mutual information were computed using sklearn and numpy with an in-house script following previous work . Geometric coupling and hydrogen bonding analysis were computed using the cpptraj utility[136] in AMBER18 .