Recent advances in hardware and algorithms have made it possible for increasingly large proteins to be studied with a full QM treatment. These simulations have revealed the importance of first principles to accurately describing unexpected structures and to explaining charge transfer and polarization in water . Proteins are not just flexible but undergo concerted changes in shape, meaning that the motions of residues (e.g., changes in positions of Ca atoms or dihedral angles) are coupled. Analysis of geometric coupling has been extensively applied to understand this conformational allostery in proteins.[106-108] However, similar analysis has only recently begun to be applied to the quantum mechanical properties of proteins in order to understand the extent to which the QM charge distribution among protein residues varies dynamically.