Code used in MATLAB and R for the purpose of generating HX difference plots and HX ribbon plots

PARP1 and PARP2 recognize DNA breaks immediately upon their formation,
generate a burst of local PARylation to signal their location, and are
co-targeted by all current FDA-approved forms of PARP inhibitors (PARPi)
used in the cancer clinic. Recent evidence indicates that the same PARPi
molecules impact PARP2 differently from PARP1, raising the possibility
that allosteric activation may also differ. We find that unlike for PARP1,
destabilization of the autoinhibitory domain of PARP2 is insufficient for
DNA damage-induced catalytic activation. Rather, PARP2 activation requires
further unfolding of an active site helix. In contrast, the corresponding
helix in PARP1 only transiently forms, even prior to engaging DNA. Only
one clinical PARPi, Olaparib, stabilizes the PARP2 active site helix,
representing a structural feature with the potential to discriminate small
molecule inhibitors. Collectively, our findings reveal unanticipated
differences in local structure and changes in activation-coupled backbone
dynamics between human PARP1 and PARP2.