The molecules of life: from structure to chemical function

Timetable

Laboratory, 30 hours, two groups, 7 practicals, room 3.51, Szymon Krzywda

Lecture, 15 hours, 7x, room 3.52, Szymon Krzywda

Proseminar (Conversatorium/Journal club), 15 hours, 7x, room 3.52, Szymon Krzywda

Module aim (aims)

1. Understanding the structure of: components of nucleic acids and proteins, nucleic acids, protein folds and macromolecular complexes.
2. Exercise spatial imagination with an emphasis on understanding the three-dimensional structure of macromolecules and principles governing their construction.
3. Gaining knowledge about modern methods of macromolecule crystallization.
4. Acquiring skills to build models of components and nucleic acid fragments, secondary structures of proteins, and simple modeling of the structure of macromolecules.
5. The ability to use global information resources on the structure of macromolecules.
6. Ability to assess the quality of the macromolecular model; sensitivity to matters of scientific reliability.

Pre-requisites in terms of knowledge, skills and social competences (where relevant)

Basic course of organic chemistry or biochemistry.

Syllabus

Auditorium lectures

1. Principles of protein structure.
2. Classification of protein folds.
3. Anatomy and taxonomy of nucleic acids and macromolecular complexes.
4. Overview of experimental methods of structural biology: cryo-EM.
5. Principles of macromolecular crystallography.
6. Protein handling and crystallization.
7. Phasing methods in macromolecular crystallography.
8. Electron density maps and model building.
9. Protein Data Bank (PDB) and model validation.
10. Examples of structure-based drug design.

Laboratory practicals

• Symmetry, point & space groups, intl notation, enantiomorphism and spereoscopy.
• Protein and DNA model building - construction of models of protein secondary structure and B-DNA (two practicals).
• Electron density maps and their interpretation.
• Protein structure refinement and validation.
• PDB and bioinformatics tools for protein analysis.
• An exercise in structure-guided drug design.

Journal club

• Meetings with student seminars presenting assignments from current literature with discussion.

Reading list

• Branden, J. Tooze: Introduction to Protein Structure, 2nd edition, Garland Publishing , 1999
• Rhodes, Crystallography Made Crystal Clear, 3rd edition, Academic Press 2006
• Rupp, Biomolecular Crystallography, Garland Science 2010
• Liljas, Textbook of Structural Biology, World Scientific Publishing 2009
• Lesk, Introduction to Protein Science: Architecture, Function, and Genomics, Oxford U. Press 2010