Quantitative Biosciences Thesis Proposal 

Ngoc Phuong Dung Ho
School of Chemistry and Biochemistry

Advisor: Advisor: James C. Gumbart (School of Physics)

Open to the Community

Across Scales of Regulation: Decoding How Small Molecules Reshape Protein Dynamics, Assembly, and Phase Separation
Tuesday, September 1, 2026, at 2:00 pm 

Howey Physics Building, Room W401

Committee Members:

Jeffrey Skolnick (School of Biological Sciences)

Andrew McShan (School of Chemistry and Biochemistry)

Nael A. McCarty (Emory University)

Abstract:

Small molecules modulate essential biological processes across diverse spatial and temporal scales, from regulating intramolecular channel gating to remodeling dynamic oligomeric interfaces and dictating the mesoscale material properties of biomolecular condensates. Although structural biology has resolved numerous therapeutic binding pockets, static structures alone cannot explain how ligand binding alters the dynamic conformational ensembles that govern functional outcomes. This thesis establishes an integrated computational and biophysical framework which combines all-atom molecular dynamics, machine-learning-assisted conformational sampling, coarse-grained modeling, and experimental validation to decode small-molecule regulation across distinct biological hierarchies. By elucidating potentiator-driven gating in cystic fibrosis transmembrane conductance regulator (CFTR) channels, targeting transient dimer interfaces in tumor necrosis factor alpha (TNF-α), and resolving drug-induced single-chain collapse in fused in sarcoma (FUS) condensates, this work connects atomistic conformational shifts to emergent mesoscale organization, providing rational principles to accelerate targeted therapeutic discovery.