2.1.2. MD Studies

To study the stability of the compound **7**-VEGFR-2 complex (**7**-VEGFR-2 complex), we performed an MD simulation for the complex. The trajectory was used to extract the RMSD (Figure 6A), RMSF (Figure 6B), SASA (Figure 6C), RoG (Figure 6D), the change in the number of hydrogen bonds (Figure 6E), and the distance between the center of masses between the compound **7** and VEGFR-2 (Figure 6F). The RMSD of the protein and **7**-VEGFR-2 complex shows that the system was changing its conformation in the first half of the simulation before coming to a stable state, with an average of 5 Å and 5.46 Å, respectively. On the other hand, the RMSD of compound **7** shows fluctuations in approximately the first 65 ns, indicating some intrinsic movement of the ligand, before coming to stable values at around 3.2 Å. The reason for the increase in the RMSD after 50 ns is the large motion of the L1047:P1066 loop, as shown in the RMSF values. In addition, the terminals show very large fluctuations, reaching 8 Å. On the other hand, nearly most of the amino acids have fluctuations of less than 2 Å. The values of SASA (average = 17,370 Å2), RoG (average = 20.66 Å), and the change in the number of hydrogen bonds (average = 70 bonds) show that the VEGFR-2 conformation is stable, with no unfolding or folding occurring. The distance between the center of mass of compound **7** and VEGFR-2 indicates that compound **7** is bound to VEGFR-2 during the simulation, with an average of 8.08 Å.

**Figure 6.** *Cont*.

Ϭ ϭϬ ϮϬ ϯϬ ϰϬ

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**Figure 6.** Analyses performed on the trajectory using VMD. (**A**) RMSD values. (**B**) RMSF. (**C**) SASA values. (**D**) RoG. (**E**) Hydrogen bond changes. (**F**) Change in the distance from the center of mass of the **7**-VEGFR-2 complex.
