Poster Presentation The 48th Lorne Conference on Protein Structure and Function 2023

MDSPACE: Extracting continuous conformational landscapes from cryo-EM singleparticle datasets using 3D-to-2D flexible fitting based on Molecular Dynamicssimulation (#354)

Rémi Vuillemot 1 2 , Alex Mirzaei 1 , Mohamad Harastani 1 , Ilyes Hamitouche 1 , Léo Fréchin 3 , Bruno Klaholz 3 , Osamu Myiashita 4 , Florence Tama 5 , Isabelle Rouiller 2 , Slavica Jonic 1
  1. IMPMC, Sorbonne University, CNRS, Paris, Ile-De-France, France
  2. University of Melbourne, Parkville, VICTORIA, Australia
  3. IGBMC, Université de Strasbourg, Strasbourg, Grand est, France
  4. RIKEN Center for Computational Science, Kobe, Japan
  5. Institute of Transformative Biomolecules, Graduate School of Science, Nagoya University, Nagoya, Japan

Analyzing continuous conformational transitions of biomolecular complexes allows to determine the dynamics of the complex and is a key to understanding its functions and structure-based drug development. We present an original approach for extracting atomic-resolution landscapes of continuous conformational variability of biomolecular complexes from cryo electron microscopy (cryo-EM) single particle images. This approach is based on a new 3D-to-2D flexible fitting method, which uses molecular dynamics (MD) simulation and is embedded in an iterative conformational-landscape refinement scheme. This new approach is referred to as MDSPACE, which stands for Molecular Dynamics simulation for Single Particle Analysis of Continuous Conformational hEterogeneity. We describe the MDSPACE approach and show its performance using a synthetic dataset of ABC transporter and an experimental dataset of yeast 80S ribosome.