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.名为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及apo_mut_last_100ns.nc的文件，分别存储了聚腺苷二磷酸核糖聚合酶1（PARP1）在野生型（Wild Type, WT）或突变状态下，结合抑制剂或呈无配体（apo）形式的分子动力学生产模拟的最后100纳秒轨迹数据。例如，niraparib_wt_last_100ns.nc对应尼拉帕尼（niraparib）结合的野生型PARP1的生产模拟最后100纳秒轨迹数据，其力场参数文件与初始坐标文件分别为niraparib_wt.prmtop与niraparib_wt.inpcrd。针对热力学积分（Thermodynamic Integration, TI）模拟，ti_niraparib_apo.rst与ti_niraparib_apo.prmtop等文件对应尼拉帕尼（niraparib）处于无配体状态下的TI模拟数据，其中.prmtop文件提供力场参数，.rst文件提供初始坐标。类似地，ti_niraparib_holo.prmtop与ti_niraparib_holo.rst，以及对应鲁卡帕尼（rucaparib）和他拉唑帕尼（talazoparib）的同类文件，均用于配体结合态的TI模拟。.nmd格式文件与predominant_protein_motion.mov展示了PARP1在无配体与抑制剂结合两种状态下的主导构象运动。本数据集包含模型2模拟的最后50纳秒数据。