Discovery of selective HDAC6 inhibitors driven by artificial intelligence and molecular dynamics simulation approaches.

ABSTRACT: Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity

SUBMITTER: Liu X 

PROVIDER: S-EPMC12491706 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature