Our research is focused on the development of novel theoretical and computational methods and AI techniques, which greatly enhance computer simulations and facilitate simulation analysis, and the application of these methods, making unprecedented contributions to biomolecular modeling and drug discovery. In collaboration with leading experimental groups, we combine complementary simulations and experiments to uncover functional mechanisms and design drugs of important biomolecules, including G-protein-coupled receptors (GPCRs), membrane-embedded proteases, RNA-binding proteins, and RNA. At the interface of computational biology, chemistry, biophysics, bioinformatics and pharmacology, our research aims to address three major topics: (i) development of biomolecular enhanced sampling and AI techniques, (ii) multiscale computational modeling of critical cellular signaling pathways, and (iii) AI-driven drug discovery of medically important proteins and RNA for treatments of neurological disorders, heart failure and cancers.