{"title":"释放中医药的潜力:利用CSLN和分子动力学发现药物靶点的计算方法。","authors":"Qi Geng, Pengcheng Zhao, Zhiwen Cao, Zhenyi Wu, Changqi Shi, Lulu Zhang, Lan Yan, Xiaomeng Zhang, Peipei Lu, Jianyu Shi, Cheng Lu","doi":"10.1007/s11030-025-11177-8","DOIUrl":null,"url":null,"abstract":"<p><p>The diverse chemical components of traditional Chinese medicine (TCM) exhibit significant therapeutic potential; however, the action mechanisms of these compounds often remain unclear. The use of drug-target prediction can aid in identifying the specific targets of TCM, thereby revealing their bioactivity and mechanisms. The efficiency, cost-effectiveness, and powerful predictive capabilities of artificial intelligence algorithms have led to their emergence as effective tools for accelerating drug-target interaction analysis. To systematically investigate TCM interaction mechanisms, we integrated cosine‑correlation and similarity‑comparison of local network (CSLN) and molecular dynamics (MD) simulations. The CSLN algorithm predicts that 11-beta-hydroxysteroid dehydrogenase-1 (HSD11B1) serves as a common target for the synergistic effects of triptolide (TP) and glycyrrhizic acid (GA). MD simulations indicate that both TP and GA can maintain stable interactions with HSD11B1 and form a common binding hot region. Surface plasmon resonance (SPR) experiments reveal that both TP and GA can effectively bind to HSD11B1, with binding constants of 29.21 μM and 31.75 μM, respectively. When used in combination, the binding constant is 5.74 μM. The combination of CSLN and MD simulations represents an effective tool for the initial analysis and simulation of interaction patterns between TCM and their targets at the computational level. These findings enhance our understanding of the interaction mechanisms between drugs.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Unleashing the potential of traditional Chinese medicine: a computational approach to discovering drug targets utilizing the CSLN and molecular dynamics.\",\"authors\":\"Qi Geng, Pengcheng Zhao, Zhiwen Cao, Zhenyi Wu, Changqi Shi, Lulu Zhang, Lan Yan, Xiaomeng Zhang, Peipei Lu, Jianyu Shi, Cheng Lu\",\"doi\":\"10.1007/s11030-025-11177-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The diverse chemical components of traditional Chinese medicine (TCM) exhibit significant therapeutic potential; however, the action mechanisms of these compounds often remain unclear. The use of drug-target prediction can aid in identifying the specific targets of TCM, thereby revealing their bioactivity and mechanisms. The efficiency, cost-effectiveness, and powerful predictive capabilities of artificial intelligence algorithms have led to their emergence as effective tools for accelerating drug-target interaction analysis. To systematically investigate TCM interaction mechanisms, we integrated cosine‑correlation and similarity‑comparison of local network (CSLN) and molecular dynamics (MD) simulations. The CSLN algorithm predicts that 11-beta-hydroxysteroid dehydrogenase-1 (HSD11B1) serves as a common target for the synergistic effects of triptolide (TP) and glycyrrhizic acid (GA). MD simulations indicate that both TP and GA can maintain stable interactions with HSD11B1 and form a common binding hot region. Surface plasmon resonance (SPR) experiments reveal that both TP and GA can effectively bind to HSD11B1, with binding constants of 29.21 μM and 31.75 μM, respectively. When used in combination, the binding constant is 5.74 μM. The combination of CSLN and MD simulations represents an effective tool for the initial analysis and simulation of interaction patterns between TCM and their targets at the computational level. These findings enhance our understanding of the interaction mechanisms between drugs.</p>\",\"PeriodicalId\":708,\"journal\":{\"name\":\"Molecular Diversity\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-05-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Diversity\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1007/s11030-025-11177-8\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, APPLIED\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Diversity","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s11030-025-11177-8","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
Unleashing the potential of traditional Chinese medicine: a computational approach to discovering drug targets utilizing the CSLN and molecular dynamics.
The diverse chemical components of traditional Chinese medicine (TCM) exhibit significant therapeutic potential; however, the action mechanisms of these compounds often remain unclear. The use of drug-target prediction can aid in identifying the specific targets of TCM, thereby revealing their bioactivity and mechanisms. The efficiency, cost-effectiveness, and powerful predictive capabilities of artificial intelligence algorithms have led to their emergence as effective tools for accelerating drug-target interaction analysis. To systematically investigate TCM interaction mechanisms, we integrated cosine‑correlation and similarity‑comparison of local network (CSLN) and molecular dynamics (MD) simulations. The CSLN algorithm predicts that 11-beta-hydroxysteroid dehydrogenase-1 (HSD11B1) serves as a common target for the synergistic effects of triptolide (TP) and glycyrrhizic acid (GA). MD simulations indicate that both TP and GA can maintain stable interactions with HSD11B1 and form a common binding hot region. Surface plasmon resonance (SPR) experiments reveal that both TP and GA can effectively bind to HSD11B1, with binding constants of 29.21 μM and 31.75 μM, respectively. When used in combination, the binding constant is 5.74 μM. The combination of CSLN and MD simulations represents an effective tool for the initial analysis and simulation of interaction patterns between TCM and their targets at the computational level. These findings enhance our understanding of the interaction mechanisms between drugs.
期刊介绍:
Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including:
combinatorial chemistry and parallel synthesis;
small molecule libraries;
microwave synthesis;
flow synthesis;
fluorous synthesis;
diversity oriented synthesis (DOS);
nanoreactors;
click chemistry;
multiplex technologies;
fragment- and ligand-based design;
structure/function/SAR;
computational chemistry and molecular design;
chemoinformatics;
screening techniques and screening interfaces;
analytical and purification methods;
robotics, automation and miniaturization;
targeted libraries;
display libraries;
peptides and peptoids;
proteins;
oligonucleotides;
carbohydrates;
natural diversity;
new methods of library formulation and deconvolution;
directed evolution, origin of life and recombination;
search techniques, landscapes, random chemistry and more;