Uncovering the Dynamics of Molecular Systems: Structure, Simulation, and Signal

Abstract

The primary challenge in understanding biological systems lies in deciphering the complex, multi-scale relationships between structure and function. From molecular assemblies to whole tissues, biological structures give rise to dynamic behaviors that are nonlinear, high-dimensional, and often emergent. This thesis presents a unified framework for exploring biological dynamics through three interconnected research directions. Initially, we reconstruct long-timescale biomolecular conformational changes from short simulations, bridging the gap between limited sampling and functional timescales. Next, we analyze single-molecule fluorescence (smFRET) data to reveal hidden dynamic states and transitions from noisy time-series, providing insights into transient molecular behaviors. Finally, we address protein-ligand binding by predicting ligand poses under spatial and physical constraints, generating biologically realistic conformations that capture molecular interaction dynamics. Together, these directions form a cohesive approach to modeling, learning, and interpreting biomolecular dynamics across temporal, spatial and statistical dimensions.

Date of Award	2025
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Yuan YAO (Supervisor)