Speaker: Pilar Cossio, Ph.D., Senior Research Scientist, CCM joint with CCB
Topic: Inferring molecular structural ensembles using individual cryo-EM particles
Biomolecules are inherently dynamic, and understanding their conformational ensemble distributions is essential for understanding their biological roles. Cryo-electron microscopy (cryo-EM), a technique that images individual biomolecules frozen in a thin layer of amorphous ice, has emerged as a leading method for determining the structure of biomolecules at atomic resolution. Recent advances in cryo-EM reconstruction have enabled significant progress in characterizing conformational variability around metastable states. In contrast to reconstruction, a different class of techniques has been used to infer population weights, referred to as ensemble reweighting. These methods have yet to be generalized to infer structural heterogeneity simultaneously. Here, we present a method for cryo-EM ensemble inference of molecular structures that directly infers the optimal set of structures and their associated population weights from cryo-EM images using Bayesian optimization techniques. We test the method on several systems, ranging from a four-atom toy model to an RNA molecule using real data. We find that our approach successfully recovers the molecular ensemble distribution range of experimental conditions. Our method paves the way for cryo-EM structural ensemble inference of flexible biomolecules exhibiting complex, multimodal conformational landscapes.
Speaker: Ido Lavi, Ph.D. , Associate Research Scientist, Biophysical Modeling
Topic: Dynamical arrest in active nematic turbulence
The turbulence of active nematic fluids, exemplified by microtubule–kinesin suspensions, has been widely studied in regimes populated by half-integer topological disclinations. Here, we instead investigate defect-free regimes, revealing the dramatic impact of two overlooked control parameters. First, the flow-alignment coupling is shown to enhance chaotic flows in contractile nematics while promoting a striking arrested state in extensile ones, where coherent streams are channeled through a tree-like network of nematic domain walls. Second, the ratio of the nematic healing length to the active length scale is shown to determine whether domain walls persist or instead give way to defects that dissolve them. These findings provide mechanistic insight into active nematic organization and suggest strategies for future experimental control and analysis.