Studying at York
Chemical and Structural Biology - CHE00036I
- Department: Chemistry
- Credit value: 20 credits
- Credit level: I
- Academic year of delivery: 2023-24
- See module specification for other years: 2024-25
Module will run
| Occurrence | Teaching period |
|---|---|
| A | Semester 2 2023-24 |
Module aims
This module builds directly on Stage 1 organic and biological chemistry. In the first half of the module students will be provided with an understanding of how an underpinning knowledge of organic reaction mechanisms can allow biochemists to design and synthesise biomolecules and chemical probes which can be used to elucidate biochemical processes in vivo. Focussing on how to recapitulate Nature’s syntheses of key biomolecules such as peptides and sugars using modern synthetic methods, introducing key concepts such as protecting group methodology, coupling chemistry and control of stereochemical outcomes during reactions In the second half students will then explore aspects of protein structure and function, including methods for determination of structure, which will highlight how elucidating the structural basis of protein function has had major impact on our understanding of biological function. There will be a strong emphasis on case studies and how the techniques are deployed to address specific biological and biomolecular questions.
Module learning outcomes
To reinforce knowledge of key organic reaction mechanisms including substitution reactions, amide bond formation, and carbonyl chemistry.
To describe how synthetic modification of proteins can be used to i) explore biological mechanisms and ii) construct ‘protein-small molecule’ conjugate therapeutics
Be able to design chemical routes to the synthesis of key biological molecules, including peptides and sugars
To describe how protein structure relates to protein mechanism and thus to biological function
To evaluate how the relationship between sequence, structure and function can be exploited and to model the structure of homologous proteins
To describe the basic principles of how protein structures are determined using the methods of X-ray crystallography, electron microscopy and NMR spectroscopy
To describe the wide range of functions that can be performed by proteins, such as enzymes, signalling proteins, membrane bound transport proteins and structural proteins. Students will be expected to rationalise and understand the behaviour of different proteins based on their structural features
To use case studies to develop and demonstrate their understanding of the key topics
Module content
Chemical Tools for Biology (6 lectures, 1 x 2 h unassessed workshop, MAF)
- Showcasing how synthetic logic applied to enzymology can deliver enhanced or novel reactivity for chemical and cell biology. Including in vivo/ in vitro labelling of proteins.
Synthesis of Biological Molecules (6 lectures, 1 x 2 h unassessed workshop, LIW)
- Synthesis of peptides including coupling chemistry and protecting group methodologies.
- Synthesis of sugars including protecting groups, the anomeric effect and stereochemistry/conformation.
Protein Structure, Diversity, and Fold Prediction (4 lectures, JA)
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Introduction. Essential features of protein structure. The Protein Data Bank.
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From sequence to structure, and from structure to function. Factors involved in protein folding and assembly.
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Protein evolution. Relations between proteins.
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Use of Artificial Intelligence in protein fold prediction: advantages and limitations.
Protein Crystallography (4 lectures, CH)
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Understand how X-rays interact with biological macromolecules, and the basic principles of X-ray diffraction.
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Appreciate the key experimental steps in structure determination, from growing crystals and collecting diffraction data to solving the structure.
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Using case-studies, explain how crystallography can provide mechanistic insight into the workings of a variety of macromolecular machines - from single enzymes to large multiprotein complexes.
Spectroscopic Approaches to the Study of Proteins (4 lectures, MJP)
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Appreciate the complexity of non-globular and intrinsically disordered proteins and unique features of their structural biology.
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Understand how biophysical techniques such as circular dichroism, small angle scattering and NMR spectroscopy can be applied to interrogate the structure/function relationships of proteins (and other biomacromolecules) in solution.
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Appreciate how fundamental parameters in biomolecular NMR spectroscopy such as chemical shift, j-coupling, NOE and relaxation can be used to probe the structural biology of proteins.
Electron Microscopy (4 lectures, JNB)
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Understand the main principles of electron cryo-microscopy (cryo-EM) as applied to biological problems, such as how biological samples are prepared, how they are imaged within the microscope, and how the data are processed to provide interpretable information.
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Be familiar with three prominent imaging and analysis techniques: single particle analysis, helical reconstruction, and tomography.
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Understand the major benefits and difficulties of cryo-EM and how they can respectively be leveraged and mitigated against.
1 x unassessed workshop (KDC and JA, in which Molecular Graphics will be used. It will feature Electron Density Map Fitting and the Structural Basis of Enzyme Action)
Indicative assessment
| Task | % of module mark |
|---|---|
| Closed/in-person Exam (Centrally scheduled) | 100 |
Special assessment rules
None
Additional assessment information
The exam paper has two compulsory 25-mark questions; a combined 25-mark question on the lecture courses 'Chemical Tools for Biology' and 'Synthesis of Biological Molecules' and a 25-mark question on the remaining Protein content (covering the rest of the content delivered).
Indicative reassessment
| Task | % of module mark |
|---|---|
| Closed/in-person Exam (Centrally scheduled) | 100 |
Module feedback
Results and feedback within 5 weeks. Exams are returned with question level marks and access to outline answers and markers' reports.
Indicative reading
Amino Acid and Peptide Synthesis, J. Jones
Carbohydrate Chemistry, B.G. Davis and A.J. Fairbanks
Other recommended reading is provided by the individual lectures in the form of suggested textbooks and review articles listed on hand-out material and as citations on slides.