Integrated network pharmacology and molecular simulation analysis of colchicine in coronary in-stent restenosis

Abstract

Context: In-stent restenosis (ISR) remains a major complication following percutaneous coronary intervention. Increasing evidence suggests that genetic and inflammatory mechanisms contribute to ISR pathogenesis. Colchicine has demonstrated anti-inflammatory effects in cardiovascular diseases; however, its molecular targets in ISR remain unclear. Aims: To identify potential molecular targets and signaling pathways through which colchicine may modulate ISR using integrated computational approaches. Methods: ISR-related genes were retrieved from GeneCards, OMIM, and CTD databases. Colchicine targets were predicted using SwissTargetPrediction, BindingDB, SEASearch, and DrugBank. Overlapping genes were analyzed using protein–protein interaction networks and hub gene identification. Functional enrichment analysis was performed using GO and KEGG pathways. Molecular docking and 200 ns molecular dynamics simulations were conducted to evaluate binding stability. Binding free energies were calculated using MM-GBSA. Results: Sixteen overlapping targets were identified, and ten hub genes were prioritized. Docking analysis demonstrated moderate binding affinity of colchicine toward CYP3A4, TUBB1, and CYP2B6 (−6.9 to −7.4 kcal/mol). Molecular dynamics simulations indicated stable ligand–protein complexes with RMSD values below 2.5 Å. MM-GBSA analysis suggested favorable binding energies, particularly for TUBB1. Conclusions: Colchicine was predicted to interact with several ISR-associated targets and pathways, providing a computational basis for further experimental validation.