A new horizon in the phosphorylated sites of AGA: the structural impact of C163S mutation in aspartylglucosaminuria through molecular dynamics simulation.

Exploring the mechanism of Shengmai San in treating lung adenocarcinoma based on bioinformatics and molecular dynamics simulation.

To investigate the mechanism of Shengmai San (SMS) in the treatment of lung adenocarcinoma (LUAD) based on an integrated strategy combining "network pharmacology, bioinformatics, molecular docking, and molecular dynamics simulation," aiming to provide a precise combination therapy strategy and identify potential bioactive compounds. Differentially expressed genes in LUAD were identified from the Gene Expression Omnibus database using R (originally developed at Bell Laboratories and currently managed by Lucent Technologies). SMS components (ginseng, Ophiopogon japonicus, and Schisandra chinensis) were retrieved from encyclopaedia of traditional Chinese medicine, with Lipinski-compliant compounds selected. Compound targets were predicted via SwissTargetPrediction and Similarity Ensemble Approach. Intersecting targets between differentially expressed genes and compound targets were identified for "herbs-compounds-targets-disease" network construction. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed. Hub targets were identified by analyzing the protein-protein interaction network. High-prognostic relevance targets were screened from The Cancer Genome Atlas. Compounds targeting these were identified through the herbs-compounds-targets-disease network, and absorption, distribution, metabolism, excretion, and toxicity-compliant compounds were selected using SwissADME (a web-based tool provided by the Molecular Modeling Group of the Swiss Institute of Bioinformatics). Core regulatory targets were identified through molecular docking, with complex stability assessed by molecular dynamics simulations. The key bioactive compounds of SMS for treating LUAD were identified as 7-hydroxy-2,5-dimethyl-4H-1-benzopyran-4-one, N-trans-feruloyltyramine, paprazine, and (E)-N-[(2S)-2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3-(4-hydroxyphenyl)prop-2-enamide. Hub targets included AURKA, CCNA2, CCNB1, CDK1, CHEK1, KIF11, NEK2, PLK1, TTK, and TYMS. Among these, CDK1, CHEK1, and PLK1 demonstrated both high-prognostic relevance and strong binding affinity with SMS, emerging as core regulatory targets for SMS in LUAD treatment. Mechanistically, SMS exerts its anticancer effects primarily by modulating the tumor necrosis factor, interleukin-17, cell cycle, and Lipid and atherosclerosis signaling pathways. The active components of SMS, such as paprazine, may exert antitumor effects partly through downregulating CDK1, CHEK1, and PLK1 expression. Although the present study did not examine drug-resistance models or combination regimens, our findings raise the possibility that, in patients with high expression of these genes, combining SMS with standard chemotherapy or targeted therapy could potentially enhance chemosensitivity and mitigate the development of resistance. This hypothesis, however, requires formal testing in appropriate preclinical models and functional validation studies.