Arooj Muskan, Mateen Rana Muhammad, Javed Mohsin, Ali Muhammad, Fareed Muhammad Irfan, Parveen Rukhsana, Bahadur Ali, Iqbal Shahid, Mahmood Sajid, Knani Salah, Jaber Fadi, Rahman K K Mujeeb, Alanazi Meznah M, Althobiti Randa A, Jafri Ibrahim, Amin Lamiaa Galal
Department of Life Sciences, School of Science, University of Management and Technology (UMT), Lahore, 54770, Pakistan.
Department of Chemistry, School of Science, University of Management and Technology, Lahore, 54770, Pakistan.
Sci Rep. 2025 Aug 6;15(1):28754. doi: 10.1038/s41598-025-14229-z.
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, and no of hydrogen bonds, indicated a stable protein-ligand complex.
结直肠癌（CRC）是结肠或肠道的癌症。每年报告的结直肠癌病例超过180万例，死亡85万例。这种疾病有多种遗传病因。然而，主要原因之一是KRAS基因过度表达，它可导致细胞不受控制地分裂和肿瘤发展。本研究的重点是鉴定能够抑制CRC中KRAS蛋白过度表达的潜在植物化学物质。在本研究中，从拥有17967种植物化学化合物的IMPPAT库中检索植物化学物质。根据ADMET标准对这些化合物进行进一步筛选。然后使用分子对接方法将筛选出的化合物与KRAS蛋白对接，并计算结合能。分析表明化合物-1与KRAS蛋白相互作用具有相当大的亲和力，其结合能为-9.7千卡/摩尔。此外，出于对接原因，将已获美国食品药品监督管理局（FDA）批准的抗癌药物呋喹替尼用作参考化学品。如前所述，参考化学品的结合能为-9.4千卡/摩尔。为了确定所选化合物的反应活性，进行了密度泛函理论（DFT）分析。蛋白质-配体复合物也进行了分子动力学（MD）模拟。模拟后分析，如均方根偏差（RMSD）、均方根波动（RMSF）、R以及氢键数量，表明蛋白质-配体复合物稳定。
