Fig 1.
CDK2 protein (PDB ID-6GUE).
Fig 2.
The CDK/cyclin complexes and the cell cycle phases.
Fig 3.
Workflow of the identification of phytochemicals that can effectively inhibit overexpressed CDK2 through the cheminformatics method.
Fig 4.
Chain A from the native CDK2 protein was isolated for molecular docking.
Table 1.
Identification, docking energy score, source, and therapeutic applications of the top five chosen compounds and control (fruquintinib).
Fig 5.
Molecular docking energy scores (A), 3D structures of the five best docked compounds (CID-135438111, 6474893, 10469828, 44257567, and 353825) and the control (CID-44480399) (B).
Fig 6.
ADME properties of three lead compounds (CIDs-6474893, 10469828, and 135438111) and the control (CID-44480399).
Fig 7.
Toxicity properties of the three lead compounds (CIDs-6474893, 10469828, and 135438111) and the control (CID-44480399).
Table 2.
Comprehensive analysis of intermolecular interactions and key amino acid residues involved in protein-ligand complex formation.
Fig 8.
Protein-ligand interactions between the CDK2 protein and the three lead compounds, along with the control.
CIDs-6474893 (A), 10469828 (B), 135438111 (C), and 44480399 (control) (D).
Fig 9.
Validation of docking poses of selected ligands within the binding site of the target protein.
The protein is represented in green cartoon format, with four docked ligands shown in different colors: CID-6474893 (blue, A), CID-10469828 (purple, B), CID-135438111 (cyan, C), and control CID-44480399 (yellow, D). All docked ligands are visualized in complex with the red-colored co-crystallized ligand to confirm accurate binding site alignment.
Fig 10.
The radar chart shows the post-docking MM-GBSA scores of the three lead compounds (CIDs-6474893, 10469828, and 135438111) and the control (CID-44480399).
Table 3.
Predicted biological activities of selected compounds and the control ligand with corresponding Pa and Pi values.
Table 4.
HOMO-LUMO energy gap (ΔE), molecular hardness(η), and molecular softness (S) energy score of the three lead compounds CID-6474893, 10469828, 135438111, and the control 44480399.
Fig 11.
HOMO-LUMO Gap (ΔE), HOMO, and LUMO of the three lead compounds CIDs-6474893. (A), 10469828 (B), 135438111 (C), and control 44480399 (D).
Table 5.
Three lead compounds, together with the control, produced distinct parameters, such as the greatest, smallest, and average values from the 200 ns MD simulation.
Fig 12.
Protein and ligand RMSD, RMSF, Rg, SASA, and H-bonds of the ligand-protein complex of CIDs-6474893, 10469828, 135438111, and 44480399 (control), respectively (A, B, C, D, E, F).
Fig 13.
The protein–ligand interface’s diverse bonding patterns are demonstrated during the 200 ns MD simulation.
The three lead compounds, CIDs-6474893 (A), 10469828 (B), and 135438111 (C), as well as the control, CID-44480399 (D), are displayed.
Fig 14.
2D interactions of the ligand–protein complex after a 200 ns simulation.
The three lead compounds and control: CIDs-6474893 (A), 10469828 (B), 135438111 (C), and 44480399 (D) are presented here.
Fig 15.
Post-simulation MM-GBSA analysis of the three lead compounds and the control: CIDs-6474893 (A), 10469828 (B), 135438111 (C), and 44480399 (D).
Fig 16.
Comparing the eigenvalue using PCA and the variance percentage.
Each area is shown on one of three panels. PC1, PC2, and PC3 are three variants. At this location, CIDs-6474893 (A), 10469828 (B), 135438111 (C), control 44480399 (D), and apoprotein (PDB ID-6GUE) (E).
Fig 17.
DCCM is represented by the colours blue and sea green, which signify positive and negative, respectively.
Here, CIDs-6474893 (A), 10469828 (B), 135438111 (C), 44480399 (control) (D), apoprotein (PDB ID-6GUE) (E).