Impact of V762A mutation on Poly(ADP-ribose) polymerase1 inhibition

Files named niraparib_wt_last_100ns.nc, niraparib_mut_last_100ns.nc, alaparib_wt_last_100ns.nc, talaparib_mut_last_100ns.nc, rucaparib_wt_last_100ns.nc, rucaparib_mut_last_100ns.nc, apo_wt_last_100ns.nc, and apo_mut_last_100ns.nc contain the last 100 ns of production simulations for the respective inhibitor-bound and apo forms of PARP1 in either WT or mutated states. For instance, niraparib_wt_last_100ns.nc represents the final 100 ns of production for niraparib-inhibited WT PARP1, using niraparib_wt.prmtop and niraparib_wt.inpcrd as the force-field parameter and initial coordinate files respectively. For TI simulations, files such as ti_niraparib_apo.rst and ti_niraparib_apo.prmtop correspond to TI simulations for niraparib in the apo state, where prmtop files supply parameters and rst file provide initial coordinates. Similarly, ti_niraparib_holo.prmtop and ti_niraparib_holo.rst, along with their counterparts for rucaparib and talazoparib, are used for holo-state TI simulations. The .nmd files and predominant_protein_motion.mov illustrate the dominant motion of PARP1 across both apo and inhibited states. Last 50 ns of model 2 simulations.