Biophysical Society Thematic Meeting | Trieste 2024

Emerging Theoretical Approaches to Complement Single-Particle Cryo-EM

Poster Abstracts

20-POS Board 20 MD-BASED CONFORMATIONAL INFERENCE OF SINGLE-PARTICLE CRYOEM IMAGES USING STOCHASTIC 3D RECONSTRUCTION Mao Oide 1,2 ; Chigusa Kobayashi 3 ; Yuxia Zhang 4,5 ; Satoshi Watanabe 5,6 ; Kenji Inaba 5,6 ; Yuji Sugita 2,3,7 ; 1 Osaka University, Institute for Protein Research, Suita, Japan 2 RIKEN, Cluster for Pioneering Research, Wako, Japan 3 RIKEN, Center for Computational Science, Kobe, Japan 4 Changping Laboratory, Department of New Diseases, Changping, China 5 Tohoku University, Institute of Multidisciplinary Research for Advanced Materials, Sendai, Japan 6 Kyushu University, Medical Institute of Bioregulation, Fukuoka, Japan 7 RIKEN, Center for Biosystems Dynamics Research, Kobe, Japan In single-particle cryo-electron microscopy (cryoEM), we can observe a vast number of single particle biomolecular images, each embedded in vitreous ice and consequently trapped in a conformation within a structural ensemble. These particle images enable the analysis of discrete structural heterogeneity, continuous motions, and the conformational landscape of biomolecules. Several studies have explored integrative methods using molecular dynamics (MD) simulations to support the analysis of complicated and anharmonic dynamics, such as state transitions. Typically, this type of analysis infers the conformation of each particle image by comparing it with MD structures. However, even integrative approaches struggle to handle particle images with low signal-to-noise ratios. To address this issue, we are investigating the applicability of 3D reconstruction as a denoising process prior to conformational inference. In this presentation, we will introduce our approach that incorporates stochastic 3D reconstruction into MD-based conformational inference. We will also present the application results of this method on both test and experimental cryoEM data, and discuss further challenges for its implementation.

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