CCeMMP Seminar – Prof José-Maria Carazo, Aug 29, 2023

The Flexibility of Biological Macromolecules as Revealed by Cryo-EM.

Electron Microscopy at cryogenic temperatures is currently a very well-known approach to solve the structure of biological macromolecules with sufficiently high resolution to obtain good structural models. Part of this success was the proposal of Maximum Likelihood approaches to disentangle macromolecular structural flexibility (first implemented in the software XMIPP and then in Relion) (1). However, it was then assumed that flexibility was discrete and that the user had to estimate the number of these discrete states, which clearly was not optimum. Nowadays, almost 15 years after this initial approach, new methods have been developed that allow us to consider continuous flexibility, opening the possibility to obtain conformational landscapes (2). In this context, Jose-Maria will present recent advances in his “Zernike3D” approach, showing how this can effectively access the whole range of macromolecular flexibility present in the cryoEM images without needing further estimations from the user.

(1) Scheres et al., Nat. Met., 2007; (2) Herreros et al., Nat. Comm., 2023

Prof. José-Maria Carazo

Biocomputing Unit, CNB-CSIC

INSTRUCT-ES, Instruct Image Processing Center, Madrid