Advanced Structural Biology

Course goals

After successful completion of the course, you are able to:

• Analyze macromolecular structures to describe chemical mechanisms in health and disease
• Examine and summarize scientific literature describing macromolecular structures and biochemical mechanisms in atomic detail.
• Generate informative images of macromolecular structures.   
• Choose between structure-determination approaches to answer questions about macromolecular mechanisms.
• Understand how X-ray diffraction and cryo-EM experimental density maps are obtained.
• Describe how macromolecular structures are constructed from experimental density maps.
• Optimize a macromolecular structure model to the experimental data.
• Evaluate the quality of a macromolecular structure model based on X-ray diffraction and electron microscopy data.
• Understand how AI methods can predict macromolecular structures and how to critically evaluate AI-generated model quality.
• Describe procedures for obtaining complexes of macromolecules with ligands and discuss their use in drug lead discovery.  

Content

In this course you will dive deeper into the analysis of macromolecular structures and structure-based function. Theory and application of protein structure determination by X-ray diffraction and electron microscopy, the two techniques currently most used for experimental structure determination, will be treated. Key concepts in biochemistry will be focused on from a structural biology perspective.

During four computer practicals (~3 hours) you will learn how to work with and analyze structural biology data and models. These consists of:
- making meaningful figures of protein structures
- processing of X-ray diffraction and cryo-EM data
- modeling and refinement of structural biology data
- AI based structure prediction

This 3^rd level course builds on level 1 & 2 biochemistry and biophysics focused courses. It will treat structural biology techniques and interpretation of protein structures in light of key biochemical and cell biology concepts. It fits well in the “Molecules and life” (red) learning path of the Chemistry curriculum and is central to the Molecular Biophysical Life Science (MBLS) curriculum. It builds on knowledge acquired during first and second level courses such as the Biomoleculaire chemie (SK-B1BMC, Chemistry), Biomolecular Chemistry (MBLS-105, MBLS) and Biophysical Methods & Structural Biology (MBLS-201, MBLS; Chemistry elective). It provides a steppingstone to the Master programs “Molecular and Cellular Life Science” and “Drug Innovation”.