Hydrogen bond frequency analysis showing key differences between macro-states.

The difference in the frequency of pair residue hydrogen bonds for macro-states M0–M3 compared to macro-state M4. Blue connections indicate that a hydrogen bond is present in at least 50% higher rate, while red connections indicate at least 50% lower rate with respect to macro-state M4. Terminal residues are colored in yellow. While significant changes in hydrogen bonding are evident across the protein, macro-states M0, 1, and 3 clearly indicate large changes in the pY+3 pocket, as well as consistent hydrogen-bonding changes linking the SH2 and LD domains.