Research
Our research is at the forefront of understanding the dynamic and multifaceted nature of biomolecules, with the ultimate aim of paving the way for innovative therapeutic solutions. Our work is driven by molecular simulations (all-atom and coarse-grained simulations), mathematical modeling, theoretical approaches, and close collaboration with our experimental partners. By integrating knowledge from statistical physics, physical chemistry, and molecular biology, our interdisciplinary research will advance the understanding of physical principles underlying complex molecular processes. Our current research focuses on intrinsically disordered proteins and biomolecular condensates formed by phase separation.
Intrinsically Disordered Proteins
Intrinsically disordered proteins (IDPs) or regions (IDRs) lack a stable or ordered three-dimensional structure; instead, they exist as flexible ensembles of conformations. Despite their lack of structured form, IDPs play crucial roles in a variety of biological processes, including cell signaling, transcription regulation, and the formation of biomolecular assemblies. Remarkably, approximately one-third of human proteins contain IDRs. The dynamic nature of IDPs enables them to interact with multiple partners, making them key players in cellular function and regulation. Our research aims to elucidate the physical principles that govern the functions of these flexible, disordered proteins.
Related research topics include:
Investigating the “sequence-ensemble-function” relationship of IDPs.
Designing small molecules and peptides to target IDPs.
Phase Separation in Biology
Phase separation is a fundamental mechanism by which cells compartmentalize biochemical reactions and processes without the need for membrane-bound organelles. This phenomenon leads to the formation of biomolecular condensates, which can concentrate specific proteins and nucleic acids to facilitate various cellular functions. Understanding the principles of phase separation is critical for elucidating how cells organize their internal environment and regulate biological activities. Moreover, dysregulation of phase separation is implicated in various human diseases, including cancers, neurodegenerative disorders, and infectious diseases. Our research seeks to uncover the molecular interactions and physical principles driving phase separation to better understand its role in health and disease.
Related research topics include:
Developing efficient coarse-grained models to study phase separation of different types of biomolecules.
Uncovering the physical principles governing the formation, material property and function of biomolecular condensates.
Figure from Zeng & Pappu, Curr. Opin. in Struct. Biol., 2023.