521-301 Protein Structure, Design & Engineering

Biochemistry 521-211, 521-212 and 521-220.

BBiomedSc students: 521-213 and 536-250.

By the end of the subject, the student should have developed an appreciation of the impact of structural biology on biomedical research and biotechnology, and also an understanding of the structural properties of proteins. The subject matter addresses how proteins fold in vivo and in vitro; how protein design and engineering is used for investigating structure-function relationships; and the challenges of producing recombinant proteins for pharmaceutical and industrial applications. The theoretical background to the major techniques used in modern protein chemistry and their applications in biotechnology will also be covered. The following topics will be presented: general properties of protein structure; the major classes and topologies of proteins; evolution of sequence, structure and function; protein folding and molecular chaperones; protein design for biotechnology; designing proteins de novo; computer-based prediction of protein fold; binding of small molecules to proteins and drug design; protein-protein interactions; transcription factors and their interactions with DNA; effects of point mutations on tertiary structure, protein stability and biological functions; and enzyme reaction kinetics. Examples from the classical and current scientific literature will include immunoglobulins and the use of molecular scaffolds, phage display and DNA shuffling techniques, amyloid fibrils and disease, transcription factors and protein mediators of signal transduction.

In addition to these specific skills, students will think critically from consideration of the lecture material and research papers, expand from theoretical principles to practical explanations through observing and reporting research literature and acquire abilities in collaborative working, while participating in group presentations.

Two 30-minute written tests held during semester (10% total); a 15-minute oral presentation or a written assignment of up to 1500 words during the semester (10%); a 3-hour written examination in the examination period (80%).

• C Branden and J Tooze, Introduction to Protein Structure. 2nd edn, Garland, 1998.