## 3 Results and Discussion
### Quantum Chemical Calculations
The HOMO and LUMO energy values of the AFB1 were similar to those obtained in the interaction with CYP3A4 (see Table 5). This similarity could be indicative that the electron density of AFB1 presents the same perturbation during the interactions inside the active site. Meanwhile, the HEM group showed similar values of chemical reactivity parameters when these were compared with the values obtained with CYP3A4. Table 8 details the \(\Delta\)N values obtained for the amino acids related to the interaction with AFB1 inside protein CYP1A2. Unlike for CYP3A4, negative values for \(\Delta\)N were found, specifically for the \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Residue** & \begin{tabular}{c} **EHOMO** \\ **(ev)** \\ \end{tabular} & \begin{tabular}{c} **ELUMO** \\ **(ev)** \\ \end{tabular} & \begin{tabular}{c} **Electron** \\ **Affinity** \\ **(ev)** \\ \end{tabular} & \begin{tabular}{c} **Ionization** \\ **Potential** \\ **(ev)** \\ \end{tabular} & \
\begin{tabular}{c} **Hardness** \\ **(ev)** \\ \end{tabular} &
\begin{tabular}{c} **Chemical** \\ **Potential** \\ **(ev)** \\ \end{tabular} \\ \hline AFB1 & \(-\)6.7195 & \(-\)2.2245 & 2.2245 & 6.7195 & 2.2787 & \(-\)4.5032 \\ THR124- & \(-\)7.0529 & \(-\)1.2218 & 1.2218 & 7.0529 & 2.9155 & \(-\)4.1373 \\ ASP313 & \(-\)9.7003 & \(-\)8.7071 & 8.7071 & 9.7003 & 0.4966 & \(-\)9.2037 \\ PHE226 & \(-\)7.0339 & \(-\)7.0202 & 0.7202 & 7.0339 & 3.1568 & \(-\)3.8771 \\ GLY316- & \(-\)7.0088 & \(-\)0.8041 & 0.8041 & 7.0088 & 3.1023 & \(-\)3.9065 \\ ALA317 & \(-\)8.9063 & \(-\)8.0998 & 8.0998 & 8.9063 & 0.4032 & \(-\)8.5030 \\ LEU382 & \(-\)7.2668 & \(-\)0.5047 & 0.5047 & 7.2668 & 3.3810 & \(-\)3.8858 \\ ILE386 & \(-\)6.9087 & \(-\)0.9583 & 0.9583 & 6.9087 & 2.9751 & \(-\)3.9335 \\ THR498 & \(-\)7.2769 & \(-\)0.7741 & 0.7741 & 7.2769 & 3.2513 & \(-\)4.0255 \\ HEM900 & \(-\)1.0552 & 0.5227 & \(-\)0.5227 & 1.0552 & 0.7890 & \(-\)0.2662 \\ \hline \hline \end{tabular}
\end{table} 
Table 7: Chemical reactivity parameters of amino acids present in the active site of CYP1A2 (2 HI4 PDB ID) provided by the interaction with aflatoxin AFB1. Figure 6: Schematization of the transferred electron values (\(\Delta\)N) calculated for the interactions between AFB1 and the CYP3A4 protein. (**A**) ITQN, (**B**) 2V0M, (**C**) 1W0E, and (**D**) 4 NY4. Values in red indicate electron donors. aspartic acid residues that acted as electron acceptors. The rest of the amino acids presented electron donor behavior with positive \(\Delta\)N values (see Figure 7). It is remarkable that for all \(\Delta\)N values calculated, the HEM group presented the highest positive values, falling in the range of 0.6-0.8. This behavior was observed for each CYP450 (1A2 and 3A4), demonstrating that electron transference is taking place. This level of interaction between amino acids and ligands could be related to the charge transfer values, which means that the higher the \(\Delta\)N values, the higher the interaction between compounds [34; 35]. As was expected, the HEM group was responsible for the main interaction in the active site, with \(\Delta\)N values higher than 0.6. In the same way, the oligopeptides are second in the order of interaction with AFB1. Thus, finally, there are specific peptides with less electron donor activity contributing to the oxidative process (see Table 8). The observed differences in the interactions between CYP450 and AF, using several approaches of molecular modeling, provide a better understanding of the AF-CYP450 complex. Techniques like molecular docking and quantum chemical methods [36] and multivalent/multitargeted systems [37] are efficient approaches to determine the drug-macromolecule interactions and can lead to the design of specific drugs for the prevention or treatment for the toxicity of these aflat.