Computational screening of phytochemicals targeting mutant KRAS in colorectal cancer

Colorectal cancer (CRC) is cancer of the colon or bowel. Every year, more than 1.8 million cases of colorectal cancer are reported, with 850,000 deaths. There are several genetic causes of this disease. However, one of the main reasons is the overexpressed KRAS gene that can cause uncontrolled cell division and tumor development. The present study is focused on the identification of potential phytochemicals that can inhibit the KRAS protein from being overexpressed in CRC. For this study, phytochemicals were retrieved from the IMPPAT library, which has 17,967 phytochemical compounds. The compounds were further screened based on the ADMET criteria. The screened compounds were then docked against the KRAS protein using a molecular docking approach, and the binding energies were calculated. Indicating a considerable affinity for interacting with the KRAS protein, it was shown that compound-1 had a binding energy of -9.7 kcal/mol upon analysis. Furthermore, for docking reasons, the anticancer medication fruquintinib, which has been authorized by the FDA, was used as a reference chemical. A binding energy of -9.4 kcal/mol was observed for the reference chemical, as was mentioned before. To find out the reactivity of the selected compound, DFT analysis was performed. The protein-ligand complex was also subjected to molecular dynamics (MD) simulation. Post simulation analysis, such as RMSD, RMSF, R_g, and no of hydrogen bonds, indicated a stable protein-ligand complex.