Fig 2: Interfacial contacts. Amino acid residues in licorice representation that establish interfacial contacts across the TDP1–PARP1 binding interface.

Fig 3: Prediction of individual structures and the TDP1–PARP1 complex. (A) Optimized TDP1 and PARP1 full-length structures. (B) RMSD measurements showing the stability of full-length individual TDP1 and PARP1 structures. The structural stabilities of both structures were observed after ∼75 ns. (C) Predicted TDP1–PARP1 complex using optimized TDP1 and PARP1 structures at 100 ns.

Fig 4: Inhibition of the TDP1–PARP1 complex formation in the absence and presence of synthetic peptides. (A) Location of amino acid residues, used to synthesize two peptides (PT-PP1-1 and PT-PP1-2), in three dimensional (3D) complex structure. SPR sensorgrams showing concentration dependent inhibition of binding of 100 nM TDP1 to immobilized PARP1 in the absence and presence of (B) PT-PP1-1 and (C) PT-PP1-2. (D) Response values at the end of association, represented by the arrows in (B) and (C), presented as percentage bindings of 100 nM TDP1 to immobilized PARP1 in the absence and presence of synthetic peptides. SPR response values obtained for 100 nM TDP1 binding in the absence of either peptide were considered as 100% binding. Heights of bar graphs represent average and error bars are s.d. of the response values obtained from two independent set of analyte injections.

Fig 5: Hydrogen bonding and salt bridges between TDP1 and PARP1. (A) Location of amino acid residues that were predicted to establish hydrogen bonding and salt bridge in three dimensional (3D) complex structure. Distance–time plots for (B) predicted hydrogen bonding and (C), (D), and (E) for salt bridges. The atom types that are responsible for hydrogen bonding are shown inside parentheses in Fig. 5B for each predicted amino acid residue. The same light-colored data in Fig. 5B–E correspond to distance–time measurements from different runs with the average values shown in dark colors.