Table 1.
Primary selection criteria for similar structure compounds.
Fig 1.
(A) The Crystal Structure of AChE Retrieved from RSCB-PDB, (B) the I-tasser predicted structure, and (C) the merged RCSB-PDB and predicted structures. The resolved missing residues and the conservation of the protein structure compared to its actual PDB sequence are shown.
Table 2.
The docking, redocking and ADME results of Rivastigmine’s similar structure with CID and chemical name.
Table 3.
The Docking and redocking results of tacrine’s similar structures with CID and chemical name.
Table 4.
The Docking and redocking results of galantamine similar structure with CID and chemical name.
Table 5.
The Docking results of phytochemicals with CID and chemical name.
Table 6.
Docking site analysis for selected chemicals.
Fig 2.
A visual representation of Protein-ligand interaction.
The protein-ligand interaction of Complex_1 (A), Complex_2 (B), Complex_3 (C), Complex_4 (D), Complex_5 (E), Complex_6 (F), Complex_7 (G), and Complex_8 (H). All the interactions have common Tyr123 with a hydrogen bond and Trp85 with Pi-allyl interaction. The rest of the interactions have Pi-sigma with similar residues of the active side.
Fig 3.
A visual representation of the binding pocket and ligand interaction.
(A) The 3D Structure of protein-ligand complex and protein hydrophobicity mapping. Close view of Complex_1 (B), Complex_3 (C), Complex_6 (D). The protein pocket region is slightly bluish which indicates partially hydrophilic. All the ligands bind to the same side of the protein.
Fig 4.
A 100-nanosecond simulation is conducted to measure the root mean square deviation (RMSD) results of three complexes.
Complexes 1, 3, and 6 are subjected to be a better binding stability over the 100-nanosecond molecular dynamics simulation using the Desmond software. (A) RMSD of Complex_1, (B) RMSD of Complex_3, and (C) RMSD of Complex_6. The root means square deviation (RMSD) between the ligand and protein exhibits temporal constancy, thereby ensuring stability. Nevertheless, complex_1 and 3 demonstrate persistent stability, suggesting that the interaction between the protein and ligand remains intact throughout the entire duration. Complex_6 exhibits a deviation of 30ns, indicating inferior stability compared to the other 2 complexes. Nevertheless, the overall binding interaction is not significantly unfavourable, and further investigation is required for the other parameters.
Fig 5.
The root means square fluctuation (RMSF) of all the simulation complexes over a 100-nanosecond simulation.
(A) Root Mean Square Fluctuation (RMSF) of Complex_1, (B) RMSF of Complex_3, and (C) RMSF of Complex_6. The interpretation of the results is justified. Several significant fluctuations. The fluctuation primarily arises when the ligand interacts with the protein residues. Complex_1 exhibits three significant fluctuations on the green vertical bar, which signify the contact between the ligand molecule and the protein. Complex_3 and Complex_6 exhibit significant temporal fluctuations. The overall comparison reveals significant fluctuations, although they do not exceed 4.8 AÅ.
Fig 6.
A 100ns simulation of ligand properties of all the complexes.
(A) Ligand Gyration, (B) Ligand SASA, (C) Ligand Polar Surface Area (PSA), and (D) Molecular Surface Area (MolSA). Values of complex_1, complex_3, and complex_6 are represented with blue, orange, and green colours, respectively.
Fig 7.
PCA analysis of three complexes.
The PCA of Complex_1 (A), complex_2 (B), and complex_3 (C). The White dot here mentions the transition state of protein-ligand simulation confirmation, the blue dot with a scattered indicates energetically unstable conformational states and the red dots indicate the stable conformational state.
Table 7.
Different PCA components chart of each of the complexes.
Fig 8.
The cross-correlation map of the C α atom pairs within the monomers of AChE is analyzed for dynamics.
The DCCM of Complex_1 (A), complex_2 (B), and complex_3 (C). The correlation coefficient (C ij) was represented using various colours. The values of Cij, ranging from 0 to 1, indicate positive correlations. Positive correlations indicate that these pairs of atoms tend to move in similar directions or have comparable behaviors during the simulation. On the other hand, negative correlations are represented by Cij values ranging from -1 to 0. Negative correlations indicate that these pairs of atoms tend to migrate in opposite directions or have contrasting behaviors during the simulation.
Table 8.
Calculated binding free energy of protein for complex_1, complex_3 and complex_6 with its component contributions (all the units are in kcal/mol).