Single-Course English 5 ECTS

Advanced protein structure engineering and analysis

Overall Course Objectives

The course will give participants deeper insight into where proteins are being solved in 3 dimensions. Participants will gain knowledge and experience in crystallization and X-ray structure determination, as well as an understanding of which statistical methods are used as validation of protein structures. You will also gain knowledge on how to download the raw X-ray data and how to independently optimize the model with the latest structure treatment programs, such as the Coot and refinement programs Phenix.
The course will provide an introduction to basic structural chemical concepts as well as applications to determine the structure of proteins. Participants will after the course be able to interpret and utilize structural chemistry results and databases and have gained a thorough task-based introduction to antibiotic binding sites, rational protein redesign, protein-protein complexes and an understanding of enzymatically active sites. You will gain insight into how to write your own script for pymol. As well as insight into how the protein structure database can be used as a biochemical tool to direct biochemical experiments or form the basis for new structure-based hypotheses. The course will also describe the new possibilities that the model prediction program alphafold2 has provided for structural biology. How alphafold2 can optimize the yield of pre-existing x-ray data and how alphafold2 is used in connection with protein complexes as well as for predicting structural bioengineering of therapeutics in applied research

Learning Objectives

  • examine and criticize the quality of an already published protein structure
  • access and download published data, for evaluation and re-refinement
  • critically evaluate and compare protein structures from the literature or databases
  • account for the building of crystalline materials in terms of symmetries and unit cells
  • describe fundamental X-ray diffraction theory and define the reciprocal lattice and relate it to the direct lattice
  • derive hypotheses for optimized protein design based on structural analysis
  • perform structural comparisons and understand the consequences of differences in data quality
  • set up a crystallization experiment and evaluate future experimental setups
  • explain how to solve a protein structure by the use of X-ray diffraction
  • evaluate alphafold models vs crystallographic experimental models
  • understand how alphafold models have promoted structural biology
  • Master refinement and validation of online crystallographic data

Course Content

Primary, secundary, tertiary and quaternary structure of proteins and other macromolecules. Analysis of molecular binding motifs, such as how to distinguish water, chloride or metals by using published diffraction data, examples of small molecule binding and catalytic active sites. Symmetry operations, crystal systems and space group notation. Experimental work with crystallization and test of crystal quality. Solving protein structures using X-ray diffraction, cryo electron microscopy and small angle scattering. Structure validation and article reading. Theory of X-ray scattering from crystals, including scripting for pymol.

Recommended prerequisites

protein chemistry, organic chemistry, physical chemistry

Teaching Method

Lectures, computer exercises and practical exercises.



It is expected that the student bring their personal computer and have approx 2gb space to install the programs needed.

Limited number of seats

Minimum: 6.

Please be aware that this course will only be held if the required minimum number of participants is met. You will be informed 8 days before the start of the course, whether the course will be held.

See course in the course database.





13 weeks




DTU Lyngby Campus

Course code 27325
Course type Candidate
Semester start Week 5
Semester end Week 19
Days Mon 13-17

7.500,00 DKK

Please note that this course has participants limitation. Read more