Department of Chemistry and Biochemistry
Physical Chemistry Seminar Series

Professor Gül Zerze, University of Houston
Hosted by Dhiman Ray

Phase Transitions from Molecular to Mesoscale: Computational Insights into Folding, Condensates, and Coacervates

Phase transitions provide a unifying framework for understanding the emergence of structure and function in molecular systems — from the folding of single RNAs to the stabilization of soft condensed phases. In this seminar, I will present computational studies that illuminate how molecular-level interactions and dynamics give rise to distinct thermodynamic and kinetic behaviors across scales.

First, I will revisit protein and RNA folding as paradigmatic examples of molecular phase transitions. Using enhanced sampling simulations, I will highlight how folding landscapes of a functional RNA pseudoknot reveal metastable states essential for biological plasticity. I will also present new evidence from full-length staphylococcal protein A (SPA) showing that its computationally and experimentally unstable behavior starkly contrasts AlphaFold’s predicted structure, emphasizing the limitations of such structure prediction tools as thermodynamic models.

Moving to mesoscale assemblies, I will discuss our efforts to model liquid–liquid phase separation in macromolecular systems, with particular attention to nonclassical nucleation mechanisms and long-timescale dynamics. I will then turn to recent simulations of PDDA–ATP coacervates, which exhibit stabilization against coalescence upon transfer to deionized water. These simulations uncover molecular mechanisms of ion ejection and interfacial restructuring, offering direct support for the formation of a kinetically arrested skin layer.

Together, these studies demonstrate how phase transitions in molecular systems are shaped not only by equilibrium thermodynamics but also by nonequilibrium conditions, molecular architecture, and solvent-mediated effects. Our results contribute to a deeper understanding of how soft matter systems self-organize and persist across chemical and biological contexts.