## 3 Results and Discussion
### Molecular Dynamics and Thermodynamics Analysis  
Initial 10 ns molecular dynamics simulations and thermodynamics analyses resulted in the following receptor-peptide pairs having the most stable end-state thermodynamics results, all based on the MMPBSA model: DR-4-Q, DR-5-Q, TNFR-1-A, and Fas-I. Complete breakdown of the molecular dynamics plots and thermodynamics analysis of all other peptides considered for molecular dynamics using both the MMGBSA and MMPBSA models are given in the Supplementary Materials. The equilibrium state of the peptide-receptor pair is explored in molecular dynamics simulations. Noted in Figure 7 are the results for the DR-4-Q system, which had the lowest MMPBSA score in the initial runs. Extending the simulation to 100 ns shows that the complex is able to fully stabilize only at t > 70 ns, where the RMSD value ranged from 3 to 3.5 nm only. These high RMSD values signify significant conformational changes in the system. A sharp rise can be seen between the 40 to 50 ns time interval, which then dips back to normal by the 50 to 60 ns mark. This may be due to transitional changes in the configuration of the system brought about by temporary conformational changes in secondary structure or changes induced by solvation. The magnitude of the RMSD is high for this system, which signifies that there is a great degree of conformational change happening to the complex, implying a high degree of flexibility. This is carried over to the RMSF and Rg values, which are about the same magnitude as that of the RMSD, again noting the high flexibility of the bonds in the system. This can be connected the presence of only a small number of Cys residues in DR4's sequence [27]. This then merits flexibility due to a lack of significant disulfide linkages within the receptor. Interestingly, the Rg plot is flatter than that of the RMSD, but the rise is reflected at the 40 to 50 ns mark. The SASA plot notes that solvents can intrude the system, which is in agreement with the flexibility notions being pointed out by the latter three parameters. Although the four main parameters are high, it can be gathered from the hydrogen bonds, hydrogen bond distribution, and minimum distance that the system is indeed just very flexible and that the complex does not dissociate. This is most salient in the minimum distance plot straddling from 0.15 to 0.25 nm and the hydrogen bond distribution staying mostly at 0.29 nm. This then confirms that at equilibrium the system can associate and can stay associated for a period of time. The theraphotoxin Q also showed the lowest MMPBSA score in the initial screening for DR-5. For the DR-5-Q system, as presented in Figure 8, a more consistent RMSD can be seen, as the graph does not have any sudden rises and dips throughout the simulation time. Apart from the peak at around 40 ns, there is a slow and steady rise in the latter part of the graph. Numerically, the RMSD values of this system only ever approach 1 nm, indicating a more rigid structure as compared to the DR-4-Q system. This is consistent with the RMSF values per atom, which never exceed the 1 nm mark, indicating less flexibility. The Rg, however, is much more in line with the Rg profile of the DR-4-Q system, where the Rg values of the system go over 2 nm. Still, the profile only ever goes between 2.5 to 2.7 nm in the latter half of the simulation time; thus, the system is able to hold its conformation. In terms of SASA, there is a similarity between the profile and numerical values of this system and the previous, which can be attributed to the fact that the same peptide was used and that DR-4 and DR-5 are similar structure-wise. Given that this is the case, solvents may intrude but cannot destroy the docked conformation. Auxiliary parameters such as hydrogen bonds, hydrogen bond distribution, and minimum distance mirror those of the DR-4-Q system in terms of profile and numerical value, ratifying the stability of the complex at equilibrium.