Instruct course on flexibility analysis using Scipion. Madrid, April 07 – 11, 2025

Venue

National Center for Biotechnology (CNB), Madrid, Spain
Madrid, April 07 – 11, 2025

Contact Us – I2PC – Instruct Image Processing Center

Overall Aims and Course Outline
Cryo-Electron Microscopy (CryoEM) has become a well-established technique for determining the three-dimensional structures of biological macromolecules. It currently achieves atomic resolution and enables the study of conformationally heterogeneous samples as well as macromolecular complexes. CryoEM complements other structural techniques such as X-ray crystallography and Nuclear Magnetic Resonance and is currently the fastest-growing technique in atomic structure depositions in public databases like the PDB.

The aim of this course is to introduce participants to the analysis of conformational flexibility/heterogeneity, a crucial step in CryoEM image processing to obtain dynamic information in the form of conformational landscapes. The I2PC has extensive experience in organizing courses on this topic, with previous editions being in high demand.

This course is intended for researchers at all levels.

Motivation for the I2PC Course on Conformational and Compositional Heterogeneity
The goal is to introduce researchers to flexibility/heterogeneity analysis, one of the most advanced areas in Single Particle Analysis (SPA). The course will cover the theory behind the most commonly used methods in the field and include hands-on practical sessions within the Scipion Flexibility Hub environment, facilitating the use of multiple tools within a single workflow.

Expected Impact for Young Researchers
Flexibility analysis in CryoEM is an emerging technique that enables the capture of different conformations of studied macromolecules. Gaining expertise in this area provides an added value for researchers with prior experience in CryoEM image processing, enhancing their analytical capabilities and understanding of the structural dynamics of biomolecules.

 

Contacts

Lead contact:
Carlos Oscar Sorzano
email. coss@cnb.csic.es

Administrative Contact:
Blanca Benitez
email: blanca@cnb.csic.es

Tutors

Marcos Gragera(MG) – Single Particle Analysis specialist, BCU/I2PC
David Herreros (DH) – Flexibility Hub head developer, BCU
Carlos-Oscar Sorzano (COS) – Group leader, BCU; Technical Director, I2PC
Slavica Jonic (SJ) – Research Director, CNRS

Registration Fee

  • Academic Registration Fee Instruct countries: Predocs & Postdosc 50€
  • Academic Registration Fee Instruct countries: Others 100€
  • Academic Registration Fee Non Instruct countries: Predocs & Postdosc 100€
  • Academic Registration Fee Non Instruct countries: Others 150€
  • Industrial Registration Fee 300€

You can fill your registration here

Agenda

 Times are expressed in CET time Zone

DAY 1: 

09:30-10:00 Introduction to Scipion
10:00 – 10:30 Introduction to macromolecular flexibility, state of the art, and Flexibility Hub 
10:30 – 11:00 Preparing the project, importing the data, and how to work with Scipion

11:00 – 11:30 Coffee break
11:30 – 12:15 HetSIREN (Theory)
12:15-13:00 HetSIREN (Practice – Hints on how to select parameters and customization for different datasets)

13:00-14:00 Lunch break
14:00-14:30 Dimensionality reduction of estimated landscapes
14:30 – 16:00: Landscape exploration: interactive tools

16:00 – 16:30 Coffee break
16:30 – 17:00 Useful tools to simplify data analysis (automatic filtering of “bad” particles, automatic clustering…)
17:00 – 17:30: End of the day

DAY 2: 

9:30 – 10:00: Review from the previous day
10:00 – 10:30: Zernike3Deep (Theory)
10:30 – 11:00: Zernike3Deep (Practice – Hints on how to select parameters and customization for different datasets)

11:00 – 11:30: Coffee break
12:00 – 12:30: Exploring continuous landscapes and differences with heterogeneous reconstruction methods
12:30 – 13:00: Understanding protein motions: visualizing of deformation fields, strain/rotation analysis, focused landscapes on regions of interest

13:00 – 14:00: Lunch break
14:00 – 14:30: Beyond motion blur: ZART and flexible refinement (Theory)
14:30 – 15:15: ZART (Practice)
15:15 – 16:00: Flexible refinement (Practice)

16:00 – 16:30: Coffee break
16:30 – 17:00: How to use ZART on a specific conformation?

17:00 – 17:30: End of the day

DAY 3: 

9:30 – 10:00: Review from the previous day
10:00 – 10:30: CryoDRGN (Theory)
10:30 – 11:00: CryoDRGN (Practice)

11:00 – 11:30: Coffee break
11:30 – 12:00: 3DVA (Theory)
12:00 – 13:00: 3DVA (Practice)

13:00 – 14:00: Lunch break
14:00 – 14:30: 3DFlex (Theory)
14:30 – 15:30: 3DFlex (Practice)
15:30 – 16:00: Analyzing the stability of conformational landscapes with FlexConsensus (Theory)

16:00 – 16:30: Coffee break
16:00 – 17:00: FlexConsensus (Practice)
17:00 – 17:30: End of the day

DAY 4: 

9:30 – 10:00: Review from the previous day
10:00 – 10:15: Introduction to ContinuousFlex (review of methods used in the workshop and historical background)
10:15 – 10:30: Hybrid/integrative methods (principle of using simulated dynamics to analyze cryo-EM/ET data) 
10:30 – 11:00: Methods for simulating dynamics (normal modes, MD simulation, NMMD)

11:00 – 11:30: Coffee break

11:30 – 12:15: MDSPACE (Theory)
12:15 – 13:00: MDSPACE (Practice – Hints on how to select parameters, dimensionality reduction of estimated landscapes, interactive tools for landscape exploration) 

13:00 – 14:00: Lunch break

14:00 – 14:30: MDTOMO (Theory)
14:30 – 15:00: MDTOMO (Practice – Hints on how to select parameters, dimensionality reduction of estimated landscapes, interactive tools for landscape exploration)
15:00 – 16:00: HEMNMA/DeepHEMNMA and HEMNMA-3D (Theory and Practice)

16:00 – 16:30: Coffee break

16:30– 17:00: Other methods in ContinuousFlex (TomoFlow, data synthesis for testing methods for conformational landscape estimation, …)
17:00 – 17:30: End of the day

DAY 5:     

9:30 – 10:00: Review from the previous day
10:00 – 11:00: Hints on defining flexibility workflows on different scenarios: Hints and examples on real/challenging cases

11:00 – 11:30: Coffee break
11:30 – 13:00: Hands-on on real data examples/One-to-one meetings between interested participants and course tutors

13:00 – 14:00: Lunch break
14:00 – 16:00: Hands-on on real data examples/One-to-one meetings between interested participants and course tutors
16:00 – 16:30: Closing remarks and end of the course