## 3 Results and Discussion
### ADMET Evaluation
Given that the peptides have low probability values, it may be construed that they are not likely to induce genetic mutations in their hosts. The magnitude and extent of the mutagenicity, and the manifestation of such mutations, is another potential area for study. hERG blockers are substances that block the human-ether-a-go-go-related-gene (hERG) K\({}^{+}\) channels responsible for cardiac repolarization. The blocking of these ion channels may increase the risk of arrhythmia, and is thus evaluated to ascertain the possibility that a drug might be potentially pro-arrhythmic [86]. In Figure 12, all peptides have hERG probability values of around 0.6, meaning that they have medium probability of blocking hERG channels and being pro-arrhythmic. This potential of theraphotoxins to be hERG blockers may be connected to the inherent property of theraphotoxins to bind and inhibit voltage-gated ion channels such as that of Na\({}^{+}\), K\({}^{+}\), and Ca\({}^{2+}\) in their prey, with some studies pointing to certain toxins from _Childrachys jingzhao_ that can inhibit the hERG channel as gating modifiers [87; 8]. Although no cases have been noted wherein tarantula bites have induced heart attacks in humans, this property must still be revisited and improved upon when engineering peptides for administration as anti-cancer drugs to minimize or fully prevent this side-effect from occurring. Drug design studies have pointed to modifications such as decreasing lipophilicity and lowering basicity to lessen the negative effect of hERG blocking [88]. Dose lethality is commonly measured with LD\({}_{50}\), which is the dose of a substance required to kill 50% of tested animals within a specified time frame. Low toxicity merits LD\({}_{50}\) values > 500 mg/kg [89]. In Figure 12, the LD\({}_{50}\) values of the theraphotoxins are significantly greater than this 500 mg/kg threshold limit, indicating that they are very much low in toxicity. In summary, the ADMET characterization of the theraphotoxins yielded favorable results in Papp, half-time life, H-HT, AMES, and LD\({}_{50}\). Areas that need to be considered for improvement include HIA, CYP, and hERG, especially the latter, as it is connected to the cardiac cycle. Modifications in these parameters are needed in order to optimize the positive effects of the administration of the peptides while minimizing the deleterious ones. This then opens up the avenue for further research on engineering theraphotoxins as effectors of death receptors. Although these results present a predominantly favorable ADMET evaluation of the theraphotoxins, there is limited available information on the ADMET evaluation of actual therapeutics being tested as activators of the extrinsic apoptotic pathway. A well-studied activator is lexatumumab, a recombinant monoclonal antibody derived from a mouse myeloma cell line that affects DR-5. Pharmacokine analysis during Phase I trials of the therapeutic showed that it is well tolerated up to 10 mg/kg for 14 days, with minimal toxicity to its hosts with various solid cancers [90]. Studies on lexatumumab showed that patients experienced fatigue, pain in the tumor site, hypokalemia, and transaminitis [91]. The therapeutic is still in its experimental stage and as such, further studies are needed to fully understand its mechanism, toxicity, and selectivity. An extensive in silico evaluation of the binding, stability, and ADMET properties of these theraphotoxins has yielded results which are both beneficial and harmful to some extent. Although the stability and thermodynamics of binding are favorable, as well as with some ADMET properties, the biggest challenge comes from improving the peptide's interactions with hERG channels, the blockage of which may incur arrhythmia. As these results are computational in nature, the results are then only theoretical in nature and should not be taken as actual proof that theraphotoxins can bind to death receptors. Apoptosis is a complex process that involves signal transductions that prime a cell for its death.