## 4 Models and Methods  
### Initial Structures  
On the basis of previous experimental studies of the Atox1 protein, the initial structure of the apo Atox1 protein (assigned as apo-Atox1 model) as the starting structure for the MD simulation was taken from the experimental structure (PDB entry 1 TL5) [21] and is shown in Figure 2a. The apo Atox1 protein with the total 68 residues consists of two \(\alpha\) helices (\(\alpha\)1: 13-26; \(\alpha\)2: 47-57) and four \(\beta\) strands (\(\beta\)1: 3-7, \(\beta\)2: 31-34, \(\beta\)3: 39-43, \(\beta\)4: 62-68). We chose the initial structures of the cisplatin, transplatin and oxaliplatin agents from the crystal structures (PDB entries 3 IWL and 1 PG9) [23,41] and the previous calculated results [42] (see Figure 2b). The initial structure of the transplatin agent + Atox1 protein complex (assigned as a TransPt + Atox1 model) for the MD simulation was taken from the X-ray crystal structure (PDB entry 3 IWL) that presents a trans conformation of platinum center [23]. The coordinates of the platinum center in this binary model were taken from the X-ray crystal structure with the TCEP ligand and a nitrogen atom of the Cys12 residue substituted by the two NH\({}_{3}\) groups. Based on the experimental suggestion on the structure of the cisplatin binding to the Atox1 protein [24,43], the initial structures of the binary CisPt + Atox1 and OxaliPt + Atox1 models used in our simulations were generated by substituting the transplatin agent of the TransPt + Atox1 model with the cisplatin and oxaliplatin agents, respectively. Similarly, for the ternary models, the initial structure of the cisplatin agent + Atox1 dimer complex (assigned as CisPt + 2 Atox1 model, a dimer involves Atox1 A protein and Atox1 B protein) for the MD simulation was taken from the X-ray crystal structure of the cisplatin + 2 Atox1 complex (PDB entry 3 IWX) [23]. Based on the CisPt + 2 Atox1 model, the initial structures of the ternary TransPt + 2 Atox1 and OxaliPt + 2 Atox1 models were generated by substituting the cisplatin agent with the transplatin and oxaliplatin agents, respectively. The missing residues Met1 and Glu68 in the CisPt + Atox1, TransPt + Atox1 and OxaliPt + Atox1 models, and the missing residue Met1 of an Atox1 protein in the CisPt + 2 Atox1, TransPt + 2 Atox1 and OxaliPt + 2 Atox1 models were repaired using the loop search method in the Swiss-Pdb Viewer ([[http://spdbv.vital-it.ch/](http://spdbv.vital-it.ch/)]([http://spdbv.vital-it.ch/](http://spdbv.vital-it.ch/)) [44,45]). Several different orientations of the platinum agents coordinating with the Atox1 protein for each model were chosen as the starting structures for our MD simulations, which provide a good test of whether our MD simulations are capable of driving significantly distinct starting structures to a non-distinguishable one when simulations reach equilibrium. For example, the RMSD values and the final average structures of the CisPt + Atox1 model starting from the two different initial structures predict the non-distinguishable results after the model simulations (see Figure S6a). Moreover, another construction method by docking the cisplatin agent to the Atox1 protein using the AutoDock program has also been employed to build the CisPt + Atox1 model [46]. The corresponding simulated results from the initial docked structure are similar to the original simulated one for the CisPt + Atox1 model (see Figure S6b). The 3 Na\({}^{+}\) and 25 Cl\({}^{-}\) counterions for the ternary CisPt + 2 Atox1 model were added to achieve electroneutrality and to satisfy the experimental ionic strength, namely 20 mM for cisplatin agent + Atox1 dimer complex [23]. Similar counterion processes are applied to other models [47]. The systems were explicitly solvated by using the TIP3P water potential inside a rectangular box large enough to ensure the solvent shell extended to 10 A in all directions.