Intermolecular interactions

The BIOVIA Discovery Studio software allows the visualization of intermolecular interactions between the ligand and the protein. Thus, it is an important tool for analyzing the results of molecular docking . (BIOVIA, 2023)

At this stage of the analysis, diagrams of the intermolecular interactions of the compounds were used to establish patterns between the binding energy values of the compounds, the amino acids involved and the types of interaction. In this way, it is possible to analyze the structural characteristics of the compounds that lead to good inhibitory potency results. For this purpose, the data of the best conformation in blind docking were used.

Figura 1: Gráfico das interações intermoleculares da Amostra 2

Source: BIOVIA Discovery Studio, 2023

The figure above is an example of how it is possible to analyze the intermolecular interactions of compounds with exotoxin A. With the data from intermolecular interactions and molecular docking , Table 1 below was established. In it, the samples with the best binding energy data are on the right and the compounds with the worst yields are on the left. The amino acids that establish interactions with each ligand were organized in the table.

Tabela 1: Relação entre compostos, aminoácidos, interações intermoleculares e docking

Source: Authors

In addition, the type of each interaction was also indicated using colors, with the figure below representing this legend. If the amino acid participates in more than one type of interaction, it was indicated with a different font color.

Figura 2: Legenda da tabela 1

Source: Authors

When analyzing the data on intermolecular interactions, it is possible to see that there is no established pattern in most amino acids. That said, it is noticeable that there are trends between the binding energy and such interactions with the residues.

1. ALA-472

   The amino acid ALA-472 established intermolecular interactions with all tested compounds, with Pi-Alkyl bonds. Therefore, this residue is important for PJ34 and the samples to position themselves in exotoxin A.

2. ALA-478

   The amino acid ALA-478 also established interactions with all ligands. Typically, the bonds were of the van der Waals force type for the samples with the best binding energy results, located in the first half of the table, such as Samples 2, 13 and 11. In the second half of the table, most of the bonds were of the Pi-Alkly type. Thus, ALA-478 is a recurring amino acid between exotoxin A and PJ34 and its derivatives, but considering the predominance of interactions with van der Waals forces, the weakest type of interactions, it is apparently not one of the main amino acids.

3. TYR-481

   The amino acid TYR-481 established intermolecular interactions of the Pi-Pi Stacked type with all ligands. Considering the strength of this interaction and its fundamental role in aromatic rings, which are present in all samples, TYR-481 appears to be essential.

4. TYR-470

   The amino acid TYR-470 also interacted with all ligands. The interactions were typically of the van der Waals type, but also had Alkyl , Pi-Pi Stacked , conventional hydrogen and Pi-Sigma interactions.

5. Sample 10

   Sample 10 had the second worst result in molecular docking . When analyzing its intermolecular interactions, it is noticeable that this compound was positioned in a part of exotoxin A that was slightly different from the other samples. In fact, despite establishing interactions with amino acids common to the other compounds, Sample 10 was the only one to maintain bonds with residues ARG-458, ASP-209, ASP-461, GLN-460, SER-459, THR-341 and THR-422, in addition to being the only one that did not interact with the amino acid ALA-519. Thus, this small difference in position may explain the unsatisfactory performance of Sample 10.

6. Sample 6

   Sample 6 had the worst performance in binding energy to exotoxin A. Like Sample 10, this compound apparently allocated to a slightly different segment of exotoxin A. Thus, even though it maintained interactions with some recurring residues, Sample 6 was the only one to establish bonds with amino acids ALA-520, ALA-523 and ALA-524.

7. van der Waals forces

   Van der Waals forces are the weakest type of intermolecular interaction among those presented. Samples 6 and 10, which had the worst performance in molecular docking , established several van der Waals interactions (respectively 11 and 10). Thus, this demonstrates that, since at least half of the interactions established by these samples are of this type, the interactions of these samples are weaker than the others. Therefore, the binding energy is worse when compared to the data set.

BIOVIA. BIOVIA Discovery Studio Visualizer . v24.1.0.23298. San Diego: Dassault Systèmes, 2023. Available at: < https://discover.3ds.com/discovery-studio-visualizer- download >. Accessed on: August 19, 2024.