Molecular Docking Analysis of Key Gene-Related Drug Candidates for Burn Injury

Abstract

Background: Although advanced therapeutic approaches have been used to improve the outcomes of burn patients, burn injuries continue to pose a life-threatening challenge. This study aimed to identify the innovative biomarkers and potential key gene-related drug candidates for burns. Method: We identified differentially expressed genes (DEGs) in the GSE182616 dataset, comparing control individuals with burn patients across various time points within 24 h. Co-DEGs were identified at specific intervals (0–2 h, 2–4 h, 4–8 h, 8–12 h, and 12–24 h) through overlapping analysis. Furthermore, key genes were found before and after DJK-5 treatment in the GSE210640 dataset. Based on these key genes, we screened key gene-related sets and subsequently predicted potential gene inhibitors through molecular docking. Result: Based on overlapping analysis of the GSE182616 dataset, 21 co-DEGs were screened, identifying 6 key genes, including integrin beta2 (ITGB2), GTPase of immunity-associated protein 6 (GIMAP6), tripartite motif-containing 22 (TRIM22), IFN regulatory factor 7 (IRF7), ubiquitin carboxyl-terminal hydrolase 15 (USP15), and mitogen-activated protein kinase 14 (MAPK14) with significant changes before and after treatment. These key genes demonstrated positive associations with inflammatory-related pathways such as the janus kinase-transducer and activator of transcription (JAK-STAT) signaling pathway, nuclear factor kappa-B (NF-κB) signaling, Toll-like receptor signaling, B cell receptor signaling, and T cell receptor signaling pathways. Additionally, these key genes were linked to immune cells including activated CD8 T cells, activated dendritic cells, mast cells, monocytes, natural killer cells, and neutrophils. Molecular docking demonstrated that compound DB08059 was a potential inhibitor of GIMAP6 and USP15. Moreover, compounds DB05442, DB14059, DB08437, and DB07186 acted as inhibitors of IRF7, ITGB2, MAPK14, and TRIM22 proteins, respectively. Conclusions: This study provided novel ideas for the underlying mechanism of key genes in burns and shared promising strategies for the treatment of burn injuries.