Selected target proteins’ 3D structures were retrieved from the RSCB PDB database at https://www.rcsb.org. In contrast, ChemSketch was used to generate the 3D structures of each ligand using data in the PubChem database (https://www.pubchem.ncbi.nlm.nih.gov). Additionally, the protein was created using the Discovery Studio 2019 program by eliminating water molecules, and Pyrx v.0.9.8 was used to minimize the energy of the ligands. Autodock Vina, included in Pyrx v.09.8, was used for docking (Trott and Olson 2010). The targeted docking approach and a parameter exhaustion limit of 50 were used. Using PrankWeb (https://prankweb.cz/) (Dávid et al. 2022), the size of the grid box was modified to the location of the amino acid residues (Table 1) based on the expected locations of the binding sites. The docking outcomes are acquired as binding affinity or affinity energy due to the compound’s interaction with the protein. Furthermore, the BioVia Discovery Studio 2019 program was used to visualize the interactions between the substances and the docked proteins.

MMPBSA.py version 16.0 is used to compute free energy (Valdés-Tresanco et al. 2021). At a temperature of 310.15 oK, 500 total frames were examined.

Protein and ligand preparation used GROMACS 2019 (Abraham et al. 2015), consisting of topological protein preparations with pdb2gmx. The force field for proteins uses AMBER99SB (Lindorff-Larsen et al. 2010). For cold ligand topologies, acpype is used. Furthermore, combining protein and ligand topology, solvation, addition of ions, equilibration, minimization and production of MD were carried out. MD production was carried out for 50,000 ps (50 ns). Using the qtGrace program, the MD interpretation is shown as a root mean square deviation (RMSD) graph for the backbone, a root mean square fluctuation (RMSF) graph for C-alpha, and a solvent-accessible surface area (SASA) graph for protein.

Redocking cannot be done because the three 3D structures of the IgA receptor protein do not have native ligands/NL, so the binding site is predicted through Prank Web. The findings of molecular docking on all samples of herbal substances revealed that practically all bioactive chemicals, particularly proteins with PDB IDs 6UE7 and 6UEA, had lower energy binding values than IgA. Only a tiny subset of ginger’s bioactive chemicals, Table 2, which interact with the 6UEA protein, have energy binding values less than -7 0.5 kcal/mol (Trott and Olson 2010). Additionally, the top six derivative compounds– 8-Shogaol, 8-Gingerol, 6-Shogaol, 6-Gingerol, 5-Shogaol, and 4-Shogaol–from the group of 13 were chosen (based on the average binding affinity/BA ranking) and proceeded for additional investigation together with positive controls.

Furthermore, Table 3 shows the binding site residues formed between the IgA receptor protein and the native ligand (NL), samples and controls. Hydrogen and hydrophobic bonds are the most dominant based on the type of bonds produced. The sample and control compounds retain the amino acid residue from the active site predicted by Prank Web.

The 3D visualization of the corresponding complexes of the IgA receptor protein with compound and control ligands is shown in Fig. 1 as the results. Because the grid box has been modified to the control redocking, which results in an RMSD < 2, the binding site and each ligand are identical to the control (Trott and Olson 2010).

The herbal component ginger has a more significant interaction potential than the control but is not as excellent as the native ligand, according to molecular docking studies. It is projected that 8Gingerol, 8-Shogaol, 6-Shogaol, 6-Gingerol, 5-Shogaol, and 4-Shogaol may target IgA receptor proteins.

The free energy value of bupropion is more harmful, according to the mmPBSA findings of a molecular dynamics simulation between human secretory immunoglobulin A and Gingerol and bupropion. Human secretory immunoglobulin A and bupropion have a free energy difference of -3.42 kcal/mol. The Bupropion chemical interacts more favorably with human secretory immunoglobulin A, as shown by free energy calculations using mmPBSA. The results match those of the molecular dynamics simulation.

RMSD is a crucial indication for assessing the structural stability of a protein since it quantifies the typical departure of a protein structure from its initial shape at a particular period. To determine the stability of human secretory immunoglobulin A in its interactions with the test substances gingerol and bupropion, a molecular dynamics simulation has been run for 50,000 ps. The Native protein (human secretory immunoglobulin A) has an RMSD of around 0.8 nm, according to MD findings. Human secretory immunoglobulin A’s interaction with the Bupropion test substance slightly reduced the RMSD value, which was 0.7 nm. On interaction with Gingerol, it slightly increased by 0.9 nm (Fig. 2). The interaction with Bupropion reaches equilibrium at about 15 ns. Thus, human secretory immunoglobulin A may have a stable interaction with Bupropion.

We also examined immunoglobulin A’s adaptability and interactions with the test substances (Fig. 3). RMSF stands for root mean square displacement and measures how each amino acid residue in a protein differs from the typical conformation. According to Huang et al. 2021, the flexibility of the residue during pressure treatment increases with residual variation. The graph of RMSF human secretory immunoglobulin A when interacting with the Gingerol test compound is similar to RMSF human secretory immunoglobulin A without a ligand. Meanwhile, the RMSF value of human secretory immunoglobulin A when interacting with Bupropion decreased. This RMSF value is consistent with the RMSD value.

The protein surface area that solvents may reach is determined by SASA analysis. As SASA values rise, relative growth may be seen (Krebs and De Mesquita 2016). The SASA value for human secretory immunoglobulin A without ligand molecules was 138.15 nm2. In contrast, while interacting with the test substances Gingerol and Bupropion, the SASA values of human secretory immunoglobulin A underwent a modest drop, measuring 135.06 nm2 and 134.67 nm2, respectively (Fig. 4).

Based on MD results for 50 ns, the Buprion compound has RMSD and RMSF values which are more stable compared to human secretory immunoglobulin A without the ligand. Thus, Bupropion may have the ability to bind to human secretory immunoglobulin A stably. To validate these in silico results, it is necessary to carry out in vitro and in vivo validation tests.