## 2 Results
### The Characteristics of Platinum Agents Combining with a Monomeric Atax1 Protein  
#### 2.1.1 The Structure Characteristics of Platinum + Atax1 Complexes  
Based on the previous studies of platinum agents, the platinum center in the cisplatin or transplatin agent connects two ammonias and two chlorides with the cis or trans conformation [30,31]. However, the platinum center in the oxaliplatin agent is coordinated by two nitrogens from 1,2-diaminecyclohexane and two oxygens from the oxalate. It is believed that the oxaliplatin agent loses the oxalate group, and retains its 1,2-diaminocyclohexane moiety in cell environments [32]. Therefore, each platinum center in all the three platinum agents has two active binding sites for combining with the Atax1 protein. The apo Atax1 protein molecule based on the NMR solution structure [21] consists of one \(\alpha\)-helical layer of \(\alpha\)2, \(\alpha\)1 with the angle of 46.6\({}^{\circ}\) between the two \(\alpha\) helices, and one \(\beta\)-sheet layer of \(\beta\)4, \(\beta\)1, \(\beta\)3, \(\beta\)2 arranging orderly from left to right, and is shown in Figure 2 with the total connection order of \(\beta\)1-\(\alpha\)1-\(\beta\)2-\(\beta\)3-\(\alpha\)2-\(\beta\)4. The two layers in the protein are almost parallel to each other. The metal-binding sites in this protein are the residue Cys12 located at the solvent-exposed \(\beta\)1-\(\alpha\)1 loop, and the residue Cys15 located at the \(\alpha\)1 _N_-terminal that connects the \(\beta\)1-\(\alpha\)1 loop. To investigate the structural characteristics of the platinum agents binding to the Atax1 protein, the CisPt + Atax1, TransPt + Atax1 and OxaliPt +Atax1 models were simulated, and the average structures extracted from the trajectories are shown in Figure 3. It is demonstrated that each platinum agent with the platinum center coordinating to the two residues Cys12/Cys15 is located at the middle of the \(\beta\)1-\(\alpha\)1 loop and the \(\alpha\)2-\(\beta\)4 loop that is a linker of the \(\alpha\)2 helix and the \(\beta\)4 strand in the Atax1 protein. Due to the differences of ligands in the three platinum agents, the ligand plane parallels to the \(\beta\)-sheet in the CisPt + Atax1 model, while is almost perpendicular to that in the TransPt + Atax1 model and forms a certain angle with the \(\beta\)-sheet in the OxaliPt + Atax1 model. As expected, the oxaliplatin agent with a large ligand binding to the Atax1 protein leads to the formation of a large binging pocket with the size of 82.6 A\({}^{2}\)/61.5 A\({}^{3}\) and  
Figure 1: Root-mean-square deviation (RMSD) values of all backbone atoms with respect to the corresponding starting structures for the simulations of **(a)** the apo-Atax1 **(light blue)**, CisPt + Atax1 **(green)**, TransPt + Atax1 **(magenta)** and OxaliPt + Atax1 **(cyan)** models; and **(b)** the CisPt + 2 Atax1 **(green)**, TransPt + 2 Atax1 **(magenta)** and OxaliPt + 2 Atax1 **(cyan)** models. the increase of the intersheet angle of \(\beta 1\) and \(\beta 3\) strands by \(\sim\)9\({}^{\circ}\) in the OxaliPt + Arox1 model over the cisplatin and transplatin agents (see Figures 4 and 5 and Discussion Section). Interestingly, the binding of the platinum agent to the Arox1 protein causes the unfolding of some residues at some \(\alpha\) helices and \(\beta\) strands, which predicts the deformation of the Arox1 protein (see Discussion Section). In particular, the oxaliplatin agent triggers the extensive deformation of the Arox1 protein due to its large ligand size. Figure 4: The representation of the pockets and the electrostatic surface potential of (**a**) the apo-Atox1 model; (**b**) the CisPt + Atox1 model; (**c**) the TransPt + Atox1 model; and (**d**) the OxaliPt + Atox1 model (**red**: negative charge; **blue**: positive charge). Figure 5: The time-dependence of the intersheet angles between the \(\beta\)1 and \(\beta\)3 strands of the Atox1 protein for the apo-Atox1 (**light blue**) and OxliPt + Atox1 (**cyan**) models.