Simulation par docking moléculaire des interactions protéine -ligand: Cas de cancer du colon

Abstract

Colorectal cancer (CRC) is one of the most common and deadly cancers worldwide. Despite the existence of targeted therapies directed against proteins involved in its progression, such as EGFR, VEGFR, and BRAF, limitations related to side effects, resistance, and high costs call for the search for new therapeutic alternatives. Our thesis presents an innovative methodology based on molecular docking for the identification of new inhibitors of key molecular targets. Using AutoDock Vina software, we evaluated the binding capacity of three natural compounds (curcumin, quercetin, and resveratrol) toward these target proteins, comparing them to reference drugs used in targeted therapies: cetuximab, regorafenib, and vemurafenib. The results revealed that quercetin binds in a stable and selective manner within the active sites of EGFR and VEGFR, with respective binding affinities of -9.0 and -9.9 kcal/mol, while resveratrol showed the strongest stability with BRAF, with a binding affinity of -9.3 kcal/mol. These interactions are reinforced through the establishment of stabilizing interaction networks, notably hydrogen bonds and hydrophobic interactions. Furthermore, the ADME properties and toxicological evaluation of the studied compounds suggest an optimal pharmacokinetic profile and reduced toxicity, supporting their therapeutic potential