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. 2023 Oct 23:10:1248885.
doi: 10.3389/fmolb.2023.1248885. eCollection 2023.

Using CADD tools to inhibit the overexpressed genes FAP, FN1, and MMP1 by repurposing ginsenoside C and Rg1 as a treatment for oral cancer

Manal Abouelwafa  1 , Tamer M Ibrahim  2   3 , Mohamed S El-Hadidi  3 , Mater H Mahnashi  4 , Amani Y Owaidah  5 , Nizar H Saeedi  6 , Hany G Attia  7 , John J Georrge  8 , Amany Mostafa  9
Affiliations

Using CADD tools to inhibit the overexpressed genes FAP, FN1, and MMP1 by repurposing ginsenoside C and Rg1 as a treatment for oral cancer

Manal Abouelwafa et al. Front Mol Biosci. .

Abstract

Oral cancer is one of the most common cancer types. Many factors can express certain genes that cause the proliferation of oral tissues. Overexpressed genes were detected in oral cancer patients; three were highly impacted. FAP, FN1, and MMP1 were the targeted genes that showed inhibition results in silico by ginsenoside C and Rg1. Approved drugs were retrieved from the DrugBank database. The docking scores show an excellent interaction between the ligands and the targeted macromolecules. Further molecular dynamics simulations showed the binding stability of the proposed natural products. This work recommends repurposing ginsenoside C and Rg1 as potential binders for the selected targets and endorses future experimental validation for the treatment of oral cancer.

Keywords: FAP; FN1; MMP1; ginsenoside C and Rg1; molecular docking; simulation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A): The interaction with FAP protein, ginsenoside C, and Rg1 showing the amino acids (B): The interaction between FN1 protein and ginsenoside C showing the amino acids (C): The interaction between MMP1 protein and ginsenoside C showing the amino acids.
FIGURE 2
FIGURE 2
(A–C): protein total residues, chain atoms, heavy atoms, and charged atoms for the four complexes.
FIGURE 3
FIGURE 3
(A–C): Root mean square fluctuation (RMSF) for four complexes in which the mean is not over 2.5 A°.
FIGURE 4
FIGURE 4
(A–C): Protein secondary structure elements (SSE); alpha shown in red and beta strands shown in blue.
FIGURE 5
FIGURE 5
(A–C): ligand properties for four ligands as root mean square (RMSD) for ligands, radius of gyration (rGYr), intramolecular hydrogen bonds (intra HB), molecular surface area (MoISA), solvent accessible surface area (SASA), and polar surface area (PSA).
FIGURE 6
FIGURE 6
(A–C): Ligand’s torsion plot.
FIGURE 7
FIGURE 7
(A–C): The ligand root mean square fluctuation (L-RMSF) for the four complexes.
FIGURE 8
FIGURE 8
(A–C): The Root Mean Square Deviation (RMSD) for the four complexes Protein RMSD: The above plot shows the RMSD evolution of a protein (left Y-axis). All protein frames are first aligned on the reference frame backbone, and then the RMSD is calculated based on the atom selection. Ligand RMSD: Ligand RMSD (right Y-axis) indicates how stable the ligand is regarding the protein and its binding pocket. In the above plot, ‘Lig fit Prot’ shows the RMSD of a ligand when the protein-ligand complex is first aligned on the protein backbone of the reference, and then the RMSD of the ligand heavy atoms is measured.
FIGURE 9
FIGURE 9
(A–C): A timeline representation of the interactions and contacts (H-bonds, Hydrophobic, Ionic, Water bridges) of all four complexes.
FIGURE 10
FIGURE 10
(A–C): Protein-ligand interactions (or ‘contacts’) are categorized into Hydrogen Bonds, Hydrophobic, Ionic and Water Bridges. Each interaction type contains more specific subtypes, which can be explored through the ‘Simulation Interactions Diagram’ panel. The stacked bar charts are normalized throughout the trajectory: for example, a value of 0.7 suggests that the specific interaction is maintained for 70% of the simulation time. Values over 1.0 are possible as some protein residue may make multiple contacts of the same subtype with the ligand.
FIGURE 11
FIGURE 11
(A–C): A schematic of detailed ligand atom interactions with the protein residues. Interactions that occur more than 30.0% of the simulation time in the selected trajectory (0.00 through 100.00 nsec).
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