## 3 Discussion
### The Structure Analysis of Platinum Agents Combining with the Monomeric and Dimeric Atox1 Protein
It can be seen from analyzing the symmetric Atox1 dimer model that the original hydrogen bonds between the residue Arg21 of the \(\alpha\)1 helix in the Atox1 A protein and the residues Gly59, Thr61 of the \(\alpha\)2-\(\beta\)4 loop in the Atox1 B protein for the CisPt + 2 Atox1 model, and between the residues Arg21, Gly59 of the Atox1 A protein and those of the Atox1 B protein for the OxaliPt + 2 Atox1 model are destroyed; nevertheless, no new interaction was detected due to the increase of interval distance between the two proteins in the symmetric model. Moreover, based on the simulation for the new CisPt + 2 Atox1 model with the platinum center binding to the two Cys12 residues of the Atox1 dimer, the similar conformational free energy of \(-\)3409 kcal/mol was obtained compared with that of \(-\)3404 kcal/mol for the original model with that binding to the two Cys15 residues. Summarily, the cis and trans conformations in the platinum agents may affect the structures of the platinum + 2 Atox1 complexes. All three ternary models present the asymmetric dimeric structures for the two Atox1 proteins, which supports the experimental suggestion [23]. Comparison on the Structural Characteristics of the Oxaliplatin + Atox1 and Oxaliplatin + 2 Atox1 Models  
Based on the average structures between a platinum-bound monomeric Atox1 protein and a platinum-bound Atox1 dimer, the difference of their structural characteristics was analyzed only for the OxaliPt + Atox1 and OxaliPt + 2 Atox1 models. For the OxaliPt + Atox1 model, because the ligand plane of the oxaliplatin agent is towards the \(\alpha\)1 and \(\alpha\)2 helices in the inside of the Atox1 protein, there exist some hydrogen bonds and hydrophobic interactions between the oxaliplatin ligand and the Atox1 protein, which contributes to stabilize the binary oxaliplatin + Atox1 complex. Nevertheless, because the ligand plane of the oxaliplatin agent for the OxaliPt + 2 Atox1 model is towards the outside of the Atox1 dimer, there does not exist any significant interaction between the oxaliplatin ligand and the Atox1 dimer, whereas the considerable contributions of the interactions have been found in the Atox1 protein-Atox1 protein interface with the formations of hydrogen bonds and hydrophobic interactions. Due to the specific binding conformations of the oxaliplatin agent in the two OxaliPt + Atox1 and OxaliPt + 2 Atox1 models, the binding pocket in the OxaliPt + Atox1 model caused by the oxaliplatin agent binding is larger by the size of 31.31 A\({}^{2}\)/26.2 A\({}^{3}\) than that in the Atox1 A protein of the OxaliPt + 2 Atox1 model. Moreover, the residues Gly13-Cys15 of the \(\alpha\)1 helix in the protein are rearranged from the \(\alpha\) helix structure to the loop conformations due to the oxaliplatin agent binding to the residues Cys12 and Cys15 for the OxaliPt + Atox1 model, however, such structural changes are not found for the OxaliPt + 2 Atox1 model. The angles between the \(\alpha\)1 and \(\alpha\)2 helices, and between the \(\beta\)1 and \(\beta\)3 strands in the OxaliPt + Atox1 model are larger by the values of \(\sim\)7\({}^{\circ}\) and \(\sim\)9\({}^{\circ}\), respectively, than those in the OxaliPt + 2 Atox1 model. These observations indicate the oxaliplatin agent binding to the monomeric Atox1 protein induces the larger deformation of the Atox1 protein over that to the dimeric Atox1 protein. Remarkably, the oxaliplatin agent binding to either the monomeric Atox1 protein or the dimeric Atox1 protein is energetically favorable to stabilize the platinum + protein complexes, while to block its DNA binding. Moreover, it was speculated that the larger unfolding of the Atox1 protein for the oxaliplatin agent binding to Atox1 may facilitate the aggregation of the Atox1 proteins due to more unfolding residues around the binding loop region and the large binding pocket in the Atox1 protein, favoring the aggregation of another protein. It supports the previous experiment results [25].