MDSPACE: Extracting continuous conformational landscapes from cryo-EM single particle datasets using 3D-to-2D flexible fitting based on Molecular Dynamics simulation

Rémi Vuillemot (1) , Alex Mirzaei (1) , Mohamad Harastani (1) , Ilyes Hamitouche (1) , Léo Fréchin (2) , Bruno P Klaholz (2) , Osamu Miyashita (3) , Florence Tama (4, 3) , Isabelle Rouiller (5) , Slavica Jonic (1)

1 IMPMC_BIBIP - Bioinformatique et BioPhysique [IMPMC]
2 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
3 RIKEN CCS - RIKEN Center for Computational Science [Kobe]
4 Nagoya University Graduate School of Science
5 Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria

This article presents 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. The article describes the MDSPACE approach and shows its performance using synthetic and experimental datasets.

Mots clés: Cryo electron microscopy (cryo-EM); molecular dynamics simulation (MD simulation); continuous conformational variability; 3D-to-2D flexible fitting; conformational landscapes; principal component analysis; single particle analysis

Domaines: Bio-informatique [q-bio.QM]; Apprentissage [cs.LG]; Modélisation et simulation; Génie logiciel [cs.SE]; Traitement des images [eess.IV]; Biologie moléculaire; Biophysique; Biologie structurale [q-bio.BM]

Rémi Vuillemot, Alex Mirzaei, Mohamad Harastani, Ilyes Hamitouche, Léo Fréchin, et al.. MDSPACE: Extracting continuous conformational landscapes from cryo-EM single particle datasets using 3D-to-2D flexible fitting based on Molecular Dynamics simulation. Journal of Molecular Biology, 2023, pp.167951. ⟨10.1016/j.jmb.2023.167951⟩. ⟨hal-03929029⟩