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1-Choose your course, 2-assess your knowledge, 3-fill in the gaps

Fundamentals

History of crystallography

Do you have any idea how long crystallography has been around? How have researchers progressed over the decades in studying crystals and solving the three-dimensional structures of biological macromolecules?
Start by answering some questions in the quiz below to test your knowledge.

History of crystallography

1- The early days

2- The following

3- The contribution of CCP4

1 / 10

How were the first three-dimensional structures such as NaCl or zinc sulfide determined?

2 / 10

Whose idea was it to carry out the first experiment in the diffraction of X-rays?

3 / 10

What are the impacts of CCP4?

4 / 10

Why are X-rays called X-rays?

5 / 10

In what year did the history of X-ray crystallography begin?

6 / 10

What are the objectives of CCP4?

7 / 10

What means CCP4 ?

8 / 10

What simple law, written in 1912, describes a condition for which there is constructive interference?

9 / 10

What was the first macromolecule structure solved in 1959 by Max Perutz?

10 / 10

In 1915, Henry Bragg wrote a famous article. What did he describe in this article?

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Quitter

History of NMR

Do you know how long NMR has been around? How have researchers used it over the decades to study the three-dimensional structures of biological macromolecules in solution?
Start by answering some questions in the quiz below to test your knowledge.

History of RMN

1 / 3

In what year was 2D NMR proposed for the first time?

2 / 3

What were the first substances to be measured by NMR (in bulk)?

3 / 3

What type of magnets were first used in NMR?

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History of electron microscopy

How did the first microscopes, and then electron microscopes, emerge? How did the development of the individual components of the microscope lead to today’s atomic spatial resolution?

History of electron microscopy

Some key dates and milestones in the evolution of microscopy, then electron microscopy

1 / 4

To generate an electron beam, modern electron microscopes use :

2 / 4

The resolution limit of an optical microscope, its resolution power, depends on :

3 / 4

The first microscope, developed by Antoni van Leeuwenhoek, produced images with a spatial resolution of

4 / 4

The first electron microscope, built in 1931 by Ernst Ruska, provided a resolution of

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Quitter

History of computing

Computing also has its history, from the very first calculators to today’s powerful machines, what has been the path taken?
Before watching the video, check your knowledge by answering the questions below.

History of computing

1 / 4

Match the technological progress with the year in which the first computers based on this progress appeared:

Miniaturisation
Printed circuit boards
Transistors
Vacuum tubes

2 / 4

In 1965, Gordon Moore stated the principle that the number of transistors should double every two years at a constant price.

3 / 4

The three binary operators used to build a computer are:

4 / 4

The word Informatics is made up by combining the two words :

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LINUX

To find out how familiar you are with the LINUX environment, start by answering the quiz questions below.

LINUX

Introduction to LINUX

1 / 4

What makes it possible to coordinate operations between different computer parts?

2 / 4

Indicate the meaning of each of these commands

mv
pwd
cd
ls

3 / 4

In 1991, Linus Torwald wrote LINUX based on a :

4 / 4

What are the main components of a computer?

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The correlation coefficient

In structural biology, we often need to compare two sets of data to assess their similarity, or to compare data with a model.
What is a correlation coefficient? What can it do in structural biology?
To see if you know what a correlation coefficient is and what it can do for you, start by answering some questions in the quiz below.

Correlation coefficient

1 / 6

True or false: Correlation coefficient can be used to compare data not on the same scale.

2 / 6

In crystallography, the cc1/2 is used to decide :

3 / 6

A cc1/2 is calculated in electron microscopy to determine the resolution limit of a Coulomb potential map:

4 / 6

In crystallography, the R-factor is used to calculate the difference between ...

5 / 6

True or false: A high correlation coefficient between two phenomena means that they are causally related.

6 / 6

The value of a correlation coefficient varies:

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The Fourier transform

In the early 19th century, Joseph Fourier developed the revolutionary idea that the sine and cosine trigonometric functions could be used to decompose any function. The transform that was named after him is a mathematical tool that can be used to understand and implement many digital signal and image processing techniques. Among its many applications, it can be found in all structural biology methods.
To find out if you are familiar with this function, and its relative the Patterson function, start by answering the questions in the quiz below.

Fourier transform

Introduction,

The phase problem,

The Patterson function

1 / 11

What are the two essential pieces of information we need to reconstruct the frequency of a periodic signal?

2 / 11

The simple sinusoidal curve that describes a periodic signal is :

3 / 11

From one or more diffraction datasets, the Patterson function provides :

4 / 11

An important property of the Patterson function is that peak height is proportional to:

5 / 11

Each structure factor calculated from the intensity of a diffraction spot is made up of :

6 / 11

En 1915, Henry Bragg understands that ...

7 / 11

In the calculation of the electron density by means of the inverse Fourier transform, the unknown is :

8 / 11

When solving a structure by crystallography, the Patterson function is used as:

9 / 11

The number of electrons at each point x, y, z of a crystal unit cell corresponds to:

10 / 11

The amplitude of each structure factor F(hkl) is calculated from the intensity I(hkl) of each index hkl. It contains information about :

11 / 11

The mathematical function used to move from reciprocal space to real space is :

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What is a protein?

Proteins are responsible for virtually all the functions of living organisms, including enzymatic functions, cytoskeletal structure, cell signalling, regulation of gene expression, etc. etc.
Find out if you know what a protein is by answering the questions below

What is a protein?

1 / 5

Enzymes are proteins whose function is to ...

2 / 5

The sequential covalent linkage of amino acids makes up the ...

3 / 5

Proteins are made up of atoms of:

4 / 5

Haemoglobin is a protein that enables the ...

5 / 5

Ribosomes, responsible for protein synthesis, are made up of ...

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What is a 3D structure?

What is a three-dimensional structure?
How can we visualise these structures?
The files that describe the atomic structure of a macromolecule are stored in an international database that is open to everyone: the Protein Data Bank.
To find out if you know what a three-dimensional (3D) structure is and how the files used to describe it are made, you can start by answering a few questions in the quiz below.

What is a three-dimensional structure?

1 / 13

What parameters are used to assess 3D structure quality?

2 / 13

Which level of structure involves interactions between the side chains of amino acid residues?

3 / 13

What functions are available in ChimeraX?

4 / 13

Which 3D structures must have their coordinates deposited in the PDB before publication in a scientific journal?

5 / 13

When editing a coordinate file for a three-dimensional macromolecule structure, what information can be found in a line that begin with the keyword ATOM:

6 / 13

When was the R-free factor introduced to assess the quality of a structure solved by X-ray crystallography?

7 / 13

Which file format(s) is (are) a standard format for saving the 3D coordinates of molecules?

8 / 13

Which of these words correspond to modes of representation of a three-dimensional model?

9 / 13

Which command below is used to import a PDB structure file into ChimeraX?

10 / 13

What file tool(s) can be used to visualise a molecular structure in 3D?

11 / 13

Which of these extensions corresponds to a standard format for coordinate files used by software for visualising the structures of biological macromolecules?

12 / 13

What information can be found in the international database of biological macromolecule structures?

13 / 13

What does the PDB acronym stand for?

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Visualize molecules with Chimerax software

How do you visualise molecules with a software tool like ChimeraX?

Introduction to ChimeraX software

How do you visualise molecules with a software tool like ChimeraX?

1 / 4

What functions are available in ChimeraX?

2 / 4

What file tool(s) can be used to visualise a molecular structure in 3D?

3 / 4

Which command below is used to import a PDB structure file into ChimeraX?

4 / 4

Which file format(s) is (are) a standard format for saving the 3D coordinates of molecules?

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Quitter

Experimental methods in structural biology

There are three main experimental methods in structural biology. On what basis should you choose one method over another?
Find out if you are familiar with these methods by answering these questions before watching the videos at the end of the quiz.

The experimental methods

Introduction to experimental methods in structural biology

1 / 6

Associate the experimental method with the corresponding property that this method exploits.

Nuclear Magnetic Resonance
Cryo-Electron microscopy
X-ray crystallography

2 / 6

Crystal diffraction analysis is carried out using :

3 / 6

What experimental methods can be used to determine the three-dimensional structure of a macromolecule at the atomic scale?

4 / 6

What is the size unit associated with the three-dimensional structure of a biological macromolecule?

5 / 6

Protein crystals :

6 / 6

The proteins studied by crystallography are generally :

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Basics of sample preparation for structural biology

Choosing the right expression system

How do you choose the best expression system for your structural biology project?
Take the quiz below to find out if you already know about the different expression systems and their advantages and disadvantages.

Choosing an expression system

1 / 5

True or false, for the production of recombinant proteins of eukaryotic origin, periplasmic expression in Escherichia coli is recommended for the production of toxic proteins.

2 / 5

Tick each box whose statement corresponds to an advantage of the cell-free expression.

3 / 5

True or false, when it comes to producing recombinant proteins of eukaryotic origin, mammalian CHO cells are good tools for the industrial production of complex proteins with specific post-translational modifications.

4 / 5

Which of these expression systems are compatible with the production of a secreted protein?

5 / 5

What cellular systems would be well suited to producing a glycosylated secreted protein?

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Know, clone, produce and purify your sample

What are the different steps and tools that are involved in the preparation of a biological sample?
Make sure you answer the following questions before you get started

Knowing, cloning, producing and purifying your sample

The first essential steps in preparing a sample

1 / 7

In order to produce a protein, the DNA fragment that contains the gene may also contain ...

2 / 7

By comparing the sequence of a protein with homologous sequences, it is possible to :

3 / 7

What chemical or electrochemical properties can be used to classify amino acid side chains?

4 / 7

Production of a protein requires prior knowledge of:

5 / 7

If, after an initial affinity purification step, the eluted solution is incubated with a specific protease, what does the solution contain at the end of the incubation?

6 / 7

Under what conditions is it possible to induce the production of a protein by the host cells?

7 / 7

The preparation of a biological sample for a structural biology study involves several steps. These include ...

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Sample preparation in practice

Whether it’s bacterial or in vitro production, how do you prepare samples in the lab?
Start by answering these questions before watching the corresponding videos.

Sample preparation in practice

1/ Cloning, production, purification

2/ In vitro expression

3/ Sample preparation for NMR

1 / 9

The in vitro translation step uses a cell extract that has to contain...

2 / 9

How is bacterial concentration measured during the production stage?

3 / 9

What is shown as a function of time on a purification monitoring chromatogram?

4 / 9

After grinding the wheat germ, we get an emulsion that looks like:

5 / 9

Preparing a protein sample using cell-free synthesis allows to:

6 / 9

At the end of transformation step, what does each pale spot on the surface of the Petri dish medium correspond to?

7 / 9

What is the typical volume required for an NMR sample in solution?

8 / 9

The steps involved in preparing wheat germ extracts include:

9 / 9

What should normally be added to a sample in H2O for NMR?

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A few applications

What is the relationship between photosynthesis and bioenergy?
How can structural biology help us better understand certain diseases and predict the impact of a mutation on their development?
How can molecular knowledge of the mechanisms developed by nature help us in our search for new energies or in understanding how genetic diseases work?
Start by answering these questions before watching the corresponding videos.

A few applications

1/ From photosynthesis to bioenergies

2/ Mutations that make you sick

1 / 9

The three-dimensional structure of photosystem II shows :

2 / 9

Looking for mutations in the BRCA1 protein makes it possible to predict the risk of developing breast cancer based on :

3 / 9

Early in Earth's history, the first photosynthetic organisms were:

4 / 9

During the photosynthesis process, the various energy conversion stages include :

5 / 9

The position of mutations in the globular domain of lamins is associated with various syndromes, including :

6 / 9

A genetic disease is caused by ...

7 / 9

Oxygen is a by-product of photosynthesis.

8 / 9

Ferredoxin, which receives electrons from photosystem I, is a real hub during photosynthesis. Depending on the needs of the photosynthetic organism, it supplies electrons to :

9 / 9

Knowing the three-dimensional structure of a protein that is associated with a genetic disease or a genetic predisposition to the development of certain types of cancer makes it possible to ...

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If you want to go further

French videos about biochemistry basis :
– Chaine Youtube Biochimie facile
– Site Top of the Prots
Pour compléter la partie sur la production des protéines, dans le MOOC Gènes sans gêne, les vidéos :
Surproduire une protéine,
Construire un vecteur recombinant
Produire une protéine recombinante
Purifier une protéine
Diversifier les stratégies et les applications
Additional english videos :
Protein expression & purification techniques : overview
Youtube channel : The bumbling biochemist
Sample preparation for Cryo-EM : conference from Lori Passmore

Prerequisites

Methods

Experimental approaches : X-ray crystallography

Overview

How does light interact with matter? How are X-rays generated? What are the characteristics of a crystal?
Before watching the corresponding videos, check your knowledge by answering these questions.

General introduction to X-ray crystallography

1 / 9

What is the nature of X-rays? They are:

2 / 9

In a synchrotron, the electron gun injects electrons into:

3 / 9

When an X-ray beam interacts with a molecule, what do the superimposed maxima of the scattered waves correspond to?

4 / 9

What happens when an X-ray beam hits an atom?

5 / 9

Why do X-rays allow us to determine the structure of molecules?

6 / 9

The minimum repeated unit of a crystal is called:

7 / 9

The mathematical relationship 2*d*sinus(theta) = n*lambda describes

8 / 9

PROXIMA1 and PROXIMA2A beamlines are dedicates to:

9 / 9

Why are copper, molybdenum, manganese and cobalt the most commonly used elements in X-ray generators?

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Sample preparation : crystallisation

You need a crystal to record an X-ray diffraction signal. But in their natural condition, the macromolecules of living organisms are not organised in crystals.
How do you get a macromolecule from a soluble, disordered state to a solid, ordered state?
Whether you’re learning the basics of theory, the classic plate-based approach or the more up-to-date use of microfluidics, before watching the appropriate videos, try to test your knowledge by answering these few questions.

Macromolecule crystallisation

1 / 13

In the field of crystallogenesis, robots are used to :

2 / 13

Which of the following compounds can be used as crystallising agents?

3 / 13

ChipX is a microfluidic chip that enables crystallization experiments using the :

4 / 13

Microseeding can be carried out using:

5 / 13

What properties affect the solubility of a protein?

6 / 13

Which of these crystallisation techniques gradually increases the concentration of the protein solution?

7 / 13

A so-called crystallization matrix screen is generally used for:

8 / 13

Crystallization experiments are observed with :

9 / 13

The supersaturation zone, where the protein solution is still clear and can lead to crystallisation, is:

10 / 13

X-ray diffraction analysis of crystals in a microfluidic chip :

11 / 13

In crystallisation, the microfluidic environment enables to :

12 / 13

The crystallisation process has two main stages:

13 / 13

To seal the plates on the tanks and create a closed system that allows vapour diffusion, we use:

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Crystal environment for data acquisition

Biological macromolecule crystals contain a large percentage of solvent and are particularly sensitive to the effects of X-rays.
How to protect the crystals during the acquisition of diffraction data? What is the environment of the crystal in the experimental hut?
Before watching the corresponding videos, check your knowledge by answering these questions.

The crystal environment

1 / 6

To freeze a crystal, we need :

2 / 6

A chiral molecule is:

3 / 6

The radiolysis phenomenon is due to :

4 / 6

Which beamlines are dedicated to the crystallography of biological macromolecules at the SOLEIL synchrotron?

5 / 6

The crystal to detector distance affects:

6 / 6

In the experimental hut, the crystal is mounted on:

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Diffraction data acquisition

What happens when the crystal diffracts X-rays? What is a diffraction data set?
Before watching the videos that try to answer these questions, check your knowledge by taking this quiz.

Diffraction data

1 / 11

Indicate in order the letters corresponding to the different steps of data processing (in the form A B C D E, each letter separated by a space):

A Intensity correction (CORRECT) ;

B Search for diffraction spots (COLSPOT) ;

C Image background processing (INIT) ;

D Image integration;

E Calculation of crystal lattice and associated symmetries.

2 / 11

If the Laue group, or the space group, is incorrectly evaluated then:

3 / 11

In order to optimise the diffraction data acquisition step, the acquisition strategy takes into account the:

4 / 11

The XDS.INP file contains:

5 / 11

When Friedel's law is satisfied:

6 / 11

Bravais networks are characterised by:

7 / 11

From the control room you can:

8 / 11

In biological crystallography, the aim of data processing is to convert diffraction images into:

9 / 11

On a diffraction image, in addition to the diffraction peaks, we can see:

10 / 11

In the case of order 2 symmetry about the b axis, if Friedel's law is respected, the equivalent positions of the reflections h, k, l are :

11 / 11

The statistical criteria for diffraction data analysis are based on:

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Solving the three-dimensional structure

How do we get from diffraction data to the electron density map? What are the main mathematical concepts involved in solving the three-dimensional structure of a biological macromolecule?
Before watching the videos, test your knowledge by answering the questions in this short quiz.

Resolution of the three-dimensional structure by crystallography

1 / 10

To solve a structure, we collect a native dataset and a second derivative dataset at a wavelength corresponding to the fluorescence peak of the heavy atom present in the crystal. The acronym for the phasing method used is:

2 / 10

To solve the phase problem in the molecular replacement method, we use:

3 / 10

If we change the contents of a crystal, say by adding a heavy atom, we cause changes in the:

4 / 10

The anomalous diffusion phenomenon is associated with :

5 / 10

When calculating a Patterson map, the Harker sections are generated from crystal symmetries. They are used to:

6 / 10

In the presence of an anomalous scatterer, the maximum signal at which Friedel's law is violated is measured at wavelength or energy:

7 / 10

In an experimental phasing, whether it involves heavy atom derivatives or anomalous diffusion, there is a phase ambiguity if we collect:

8 / 10

To position heavy atoms from a native dataset and a derivative dataset, what are the essential conditions for using Patterson's function?

9 / 10

Among these proposals, the factors influencing the result of molecular replacement are

10 / 10

In molecular replacement, the Patterson function separates the resolution of the structure into two steps:

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3D model construction and analysis

How to build a three-dimensional model from an electron density map?
What process is used to refine and then evaluate the three-dimensional model?
Before watching the videos, test your knowledge by taking this short quiz.

3D model construction and analysis

1 / 7

Phase improvement is an iterative loop that allows us to improve

2 / 7

Refinement consists of minimising the difference between the observed data and the

3 / 7

Whatever the origin of the phases, the associated errors can come from ...

4 / 7

During the refinement stages, the quality of the model is assessed using the following criteria

5 / 7

The solvent flattening approach to improving the phases involves the modification of the ...

6 / 7

In the order A, B, C, D, E, place the successive stages in the construction of the molecular model on the electron density map.

The positioning of side chains
The construction of the carbon chain
The construction of a poly-alanine model
Choosing the polypeptide chain direction
The skelettonisation

7 / 7

The electron density maps that are used for the construction, correction or analysis of the three-dimensional model can be :

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If you want to go further

If you want to learn more about the concepts presented in the introductory videos here. A large number of online courses are available on the Association Française de Cristallographie website, by following this link:
https://www.afc.asso.fr/l-association/vie-de-lassociation/axes-transverses-main/enseignement-de-la-cristallographie/doctorant?view=article&id=1506

Experimental approaches : NMR

Introduction to NMR

The three words Nuclear Magnetic Resonance contain the concepts of nucleus, magnetisation and resonance.
Before accessing the two videos introducing the general physical principles of this spectroscopy, answer the questions in this short quiz.

General introduction to NMR

1 / 6

The combined analysis of correlations for TOCSY and NOESY spectra allows to:

2 / 6

The correlations observed in a 2D spectrum allow to:

3 / 6

The frequency at which an atom resonates depends on

4 / 6

The frequency allocation process consists of :

5 / 6

The interpretation of a simple spectrum gives us information about the chemical properties of the molecule, such as :

6 / 6

The resolution of an NMR spectrum is directly proportional to:

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Sample preparation for NMR

Whether it’s NMR or another approach, whether it’s production in bacteria or in vitro, let’s see the practical side in the laboratory.
Start by answering these few questions before watching the corresponding videos.

Sample preparation in practice

1/ Cloning, production, purification

2/ In vitro expression

3/ Sample preparation for NMR

1 / 9

Preparing a protein sample using cell-free synthesis allows to:

2 / 9

At the end of transformation step, what does each pale spot on the surface of the Petri dish medium correspond to?

3 / 9

What is the typical volume required for an NMR sample in solution?

4 / 9

The steps involved in preparing wheat germ extracts include:

5 / 9

How is bacterial concentration measured during the production stage?

6 / 9

What should normally be added to a sample in H2O for NMR?

7 / 9

The in vitro translation step uses a cell extract that has to contain...

8 / 9

What is shown as a function of time on a purification monitoring chromatogram?

9 / 9

After grinding the wheat germ, we get an emulsion that looks like:

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NMR instrument

How do you record data for NMR?
Before watching this video, check your knowledge by answering these questions

NMR instrument

1 / 3

What is the purpose of the console on an NMR spectrometer?

2 / 3

At a higher magnetic field B0, ...

3 / 3

What components do an NMR spectrometer need?

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Local magnetic field

What are the characteristics of the magnetic field used in NMR? How is it modulated?
Before watching the video that answers this question, test your knowledge by answering these questions.

The local magnetic field

1 / 4

What is the effect of an inhomogeneous magnetic field B0 in NMR?

2 / 4

The magnetic field B0 of a magnet used for NMR spectroscopy ...

3 / 4

In the magnetic field of an NMR spectrometer, the CH2 and CH3 protons of ethanol...

4 / 4

What is drawn in a 1D NMR spectrum?

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Chemical shift

What is the chemical shift associated with an NMR spectrum?
Before watching the video that answers this question, check your knowledge with this short quiz.

The chemical shift

1 / 3

The chemical shift is...

2 / 3

The origin of chemical shift in NMR is :

3 / 3

How does a high density of electrons around a nucleus affect its chemical shift and resonance frequency?

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2D NMR experiment

What is a 2D NMR experiment? What information can this experiment provide?
Before watching the video that answers these questions, check your knowledge with this short quiz.

The 2D NMR experiment

1 / 3

Which statements about the 2D 1H COSY spectrum are correct?

2 / 3

Which parameter is increased when recording a COSY 2D spectrum?

3 / 3

A 2D NMR experiment is ...

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Experimental approaches : Transmission Electron Microscopy

Introduction to electron microscopy

Cryo-electron microscopy, coupled with image analysis, has been rapidly growing in recent years.
What is a transmission electron microscope? What are electron microscopy images? How can a 3D structure be reconstructed from 2D images?
Before watching the two introductory videos on cryo-EM, take this short quiz to test your knowledge.

General introduction to electron microscopy

1 / 8

The images obtained by transmission electron microscopy correspond to:

2 / 8

Analysis of the electron microscopy images enables to:

3 / 8

CryoEM stands for:

4 / 8

The different types of electron microscopes can be:

5 / 8

In electron microscopy, the image analysis of isolated particles includes:

6 / 8

A very high vacuum is required inside an electron microscope in order to:

7 / 8

The light source of an electron microscope consists of:

8 / 8

The sample is frozen for electron microscopy in order to:

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Sample preparation for CryoEM

How to prepare your sample for a Cryo-EM experiment? Which grid to use, depending on the approach chosen?
Answer these few questions to test your knowledge before viewing the videos.

Sample preparation for Cryo-EM

Test your knowledge of how to prepare a sample, a grid or a carbon deposit for a CryoEM experiment.

1 / 6

What types of biological objects can be studied using cryo-EM?

2 / 6

In negative staining, how do isolated particles appear?

3 / 6

What cryogen(s) are generally used in cryo-EM?

4 / 6

What resolution limit can we expect to achieve with isolated particles approach?

5 / 6

What are electron microscope grids made of?

6 / 6

How do you place a carbon membrane on an electron microscope grid?

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Quitter

Isolated particles

In the pipeline

Tomography

In the pipeline

Electron diffraction

In the pipeline

Helical reconstruction

In the pipeline

To go further

In the field of Cryo-EM we have not prepared any videos other than the introductory ones because there are already very comprehensive courses available.
To go further in electron microscopy and gain access to all the fundamental knowledge associated with it, we recommend Professor Grant Jensen’s courses, which are freely available.
The CryoEM 101 site may also be of interest to you for access to the basics of cryo microscopy or electron tomography.Dans le domaine de la Cryo-EM nous n’avons pas préparé de vidéos autres que celles d’introduction parce qu’il existe déjà un cours très complet.

In Silico approaches

ChimeraX software

How do you visualise molecules with a software tool like ChimeraX?

Visualising molecules using ChimeraX

How do you visualise molecules with a software tool like ChimeraX?

1 / 4

What functions are available in ChimeraX?

2 / 4

What file tool(s) can be used to visualise a molecular structure in 3D?

3 / 4

Which file format(s) is (are) a standard format for saving the 3D coordinates of molecules?

4 / 4

Which command below is used to import a PDB structure file into ChimeraX?

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Quitter

Alphafold software

Alphafold software (followed by Alphafold2 and Alphafold3) has revolutionised the world of 3D prediction. How does this software work?

The basics of Alphafold software

What are the basic concepts behind Alphafold 3D prediction software?

1 / 4

Alphafold allows the 3D structure of a protein to be determined experimentally

2 / 4

Alphafold software is used to:

3 / 4

To predict the three-dimensional structure of a protein, Alphafold software needs:

4 / 4

Potential applications for a structure predicted with Alphafold are:

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Quitter

Using Alphafold

There is no quiz here. Basically, you should know whether or not you have used Alphafold2 before.
Before you start, you need to retrieve the amino acid sequence of the protein you are studying and prepare it in a format suitable for the software. To help you do this, we recommend this very small software:
https://tubiana.github.io/uniprot_to_seq/
To get started, we recommend the video
How to use Google Colab Alphafold2 and ChimeraX
This video will guide you step by step through the use of Alphafold on the shared Colab Alphafold site.
This short tutorial can also be very useful:
Alphafold Server Demo – Google DeepMind

Analysing a structure predicted by Alphafold2

The structure predicted by Alphafold necessarily contains errors. The following video can help you import the structure into ChimeraX and edit the errors estimated by Alphafold:
How to show AlphaFold error estimates with ChimeraX

A few hands-on exercises

To practise, videos are not enough. Here are some links to sites that suggest an approach to follow, or practical work.

For example, here is a wiki site that is quite comprehensive in the sense that it explains the procedure to be followed: does the experimental structure exist, if not, is it already in AlphaFoldDB, if not, which tools to use for prediction, etc. ..:
Tutorial on the use of Colabfold on proteopedia
With a link to the Google Colab page.

A practical exercise to help you understand AlphaFold output:
Understanding AlphaFold Results – Exercises

To go further in 3D Predictions

Alphafold

For more information on Alphafold software, particularly the latest version Alphafold3, we recommend this ‘New&views’ from the journal Nature.

Foldscript

Once you’ve used Alphafold 2 or 3, it can be difficult to choose the right model. Thanks to a complete, automated analysis, the FoldScript web server provides you with a summary of information that can help you choose the most relevant and accurate model. This analysis can be refined by introducing experimentally known interaction data.

Numerical simulation

In the pipeline

Complementary experimental methods

Small Angle X-ray Scattering

Small-angle X-ray scattering (SAXS) can be used to obtain structural information about macromolecules in solution. What are the basics of this method, which complements ‘conventional’ experimental methods?
Before watching the introductory video on SAXS, take a moment to test your knowledge by answering these questions.

Small Angle X-ray Scattering

1 / 4

The theoretical aspects of small-angle scattering are similar to those of :

2 / 4

SAXS provides direct information about the object:

3 / 4

SAXS curve interpretation allows to:

4 / 4

In order to properly measure the small-angle scattering of a sample in solution, you need:

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