## 3 Discussion  
### The Structure Analysis of Platinum Agents Combining with the Monomeric and Dimeric Atox1 Protein  
Base on the average structure and the trajectory analysis, the distinct differences of structures in the CisPt + Atox1, TransPt + Atox1, and OxaliPt + Atox1 models have been found. Due to the protein binding sites located at the \(\alpha 1\)\(N\)-terminal and the \(\beta 1\)-\(\alpha 1\) loop for the three models, the centroid distances between the \(\beta 1\) strand and \(\alpha 1\) helix have been analyzed to address the structural differences. It can be seen that such distance change from the average value of 13.5 A in the apo-Atox1 model to 14.0 A only in the OxaliPt + Atox1 model. However, such change is insignificant for the CisPt + Atox1 and TransPt + Atox1 models. In particular, in the OxaliPt + Atox1 model, the diaminocyclohexane plane of the oxaliplatin agent forms a certain angle with the \(\beta\)-sheet, and tilts up. The ligand of oxaliplatin agent is located at the \(\alpha 1\)\(N\)-terminal and the \(\alpha 2\)\(C\)-terminal, which causes the movement of \(\alpha 1\) helix close to the \(\beta\)-sheet and away from the \(\alpha 2\) helix, itself bend of \(\alpha 1\) helix, and the increase of intersheet angle of \(\beta 1\) and \(\beta 3\) strands by \(\sim\)9\({}^{\circ}\) (see Figure 5) compared with that in the apo-Atox1 model. While the ligand plane is parallel to the \(\beta\)-sheet in the cisplatin agent of the CisPt + Atox1 model, and is perpendicular to  
Figure 8: _Cont._that in the transplatin agent of the TransPt + Atox1 model. However, the binding of the cisplatin and the transplatin agents to the Atox1 protein in the CisPt + Atox1 and TransPt + Atox1 models does not cause any change of the intersheet angle between the \(\beta\)1 and \(\beta\)3 strands over that in the apo-Atox1 model due to the small sizes of the ligands in the two agents. To investigate the structural characteristics of the Atox1 protein, the interhelical angles of the \(\alpha\)1 and \(\alpha\)2 helices in the apo-Atox1, CisPt + Atox1, TransPt + Atox1 and OxaliPt + Atox1 models have been quantitatively examined over the simulation times by using the program INTERHLX and are shown in Figure 9. The average interhelical angle values are 46.6\({}^{\circ}\), 41.6\({}^{\circ}\), 48.5\({}^{\circ}\) and 54.1\({}^{\circ}\) for the apo-Atox1, CisPt + Atox1, TransPt + Atox1 and OxaliPt + Atox1 models, respectively, which presents the oxaliplatin agent causes larger extension of the \(\alpha\)1 and \(\alpha\)2 helices with the largest interhelical angle value. Interestingly, the large arc formed by the loop region (consisting of the residues Asp9-Gly14) linking \(\alpha\)1 and \(\beta\)1 in the CisPt +Atox1 model causes the decrease of the interhelical angle of \(\alpha\)1 and \(\alpha\)2 compared with that in the apo-Atox1 model. Oppositely, the small arc formed by the same loop region in the TransPt + Atox1 and OxaliPt + Atox1 models causes its increase. It's evident that the residues Gly13/Gly14 of \(\alpha\)1 helix, Val62 of \(\beta\)4 strand for the CisPt + Atox1 model, the residues Gly13/Gly14 for the TransPt + Atox1 model, and the residues Gly13-Cys15/Val62 for the OxaliPt + Atox1 model are rearranged from the \(\alpha\) helix or \(\beta\) strand structure to the loop conformations due to the platinum agents binding to the residues Cys12 and Cys15. Moreover, the destruction of the hydrogen bonds between the residues Gly13 and Cys15 of the \(\alpha\)1 helix in the Atox1 protein from total occupancies of simulation times of 35.3% in the apo-Atox1 model to the occupancies of 11.2% and 0% in the TransPt + Atox1 model and CisPt + Atox1/OxaliPt + Atox1 models, respectively, also supports the deformation of the Gly13-Cys15 from the \(\alpha\) helix to the loop conformations. These results presented that the oxaliplatin agent binding causes an extensive unfolding of the Atox1 protein due to more unfolding residues in the binary complex.