| Code |
15046
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| Year |
1
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| Semester |
S2
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| ECTS Credits |
5
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| Workload |
TP(40H)
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| Scientific area |
Biomedicina/Medicina/Bioquímica
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Entry requirements |
Not applicable.
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Learning outcomes |
Upon successful completion of the curricular unit of Advanced Courses V - Medical Structural Biology, the student should be able to:
1- Outline the main computational biochemistry techniques for molecular simulation in protein systems.
2- Use the methods of analysis of protein-protein and protein-ligand interactions in the validation of kinetic and thermodynamic parameters of biomolecules in solution.
3– Analyze nucleic acid-ligand interactions via laboratory techniques for selection of target molecules and structural studies.
4- Identify, by liquid chromatography, characteristics of a preparative and structurally innocuous technique in the separation of a complex mixture of proteins.
5- Describe the methods for determining three-dimensional structures of biomolecules with therapeutic relevance: nucleic acids and proteins.
6- Research and critically analyze scientific articles related to the topics taught in the course.
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Syllabus |
1- Computational Biochemistry Module- A) Methodologies; B) Molecular Mechanics; C) Molecular Dynamics Simulations. 2- Biophysical Module in Biomolecular Recognition – A) Protein-protein and protein-binding interactions by: Microcalorimetry and Surface Plasma Resonance (SPR) using an optical biosensor; B) Nucleic acid-ligand interactions: Circular Dichroism Spectroscopy to analyze the stability of DNA and RNA and determination of affinity and kinetics of the reaction between biomolecule-ligand by SPR in order to select the ligands. 3- Structural Biology Module – A) Strategies in the separation of proteins by liquid chromatography; B) Co-crystallization and Protein Soaking; Small Angle X-Ray Scattering (SAXS); X-ray Crystallography: structure determination, model refinement and functional interpretation; C) Cryoelectron Microscopy (Cryo-EM): Fundamentals, Image formation methods, Samples (mechanical, chemical, ionic milling) and resolution.
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Main Bibliography |
1- Vuorinen E et al; “Sensitive Label-Free Thermal Stability Assay for Protein Denaturation and Protein–Ligand Interaction Studies.” Analytical Chemistry, 2020, 92 (5), 3512-3516. DOI: 10.1021/acs.analchem.9b05712
2- Paul A. et al., “Biosensor-Surface Plasmon Resonance: Label-Free Method for Investigation of Small Molecule-Quadruplex Nucleic Acid Interactions.” Methods in molecular biology (Clifton, N.J.), 2019, 2035, 63–85. https://doi.org/10.1007/978-1-4939-9666-7_4
3- Alexander W., Zbigniew D., Mariusz J.; “Protein Crystallography - Methods and Protocols”, 2017, Part of the Methods in Molecular Biology book series (MIMB, volume 1607), Springer.
4- Walter Filgueira de Azevedo Jr.; “Docking Screens for Drug Discovery”, 2019, Part of the Methods in Molecular Biology book series (MIMB, volume 2053), Springer.
5- Ângela Sousa e Luís Passarinha; "Advanced Methods in Structural Biology", 2023, Springer Protocols.
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Teaching Methodologies and Assessment Criteria |
The activities carried out in the Advanced Course V are primarily based on the active participation of students in: tutorials for guided research of information, discussion and resolution of case studies proposed by the professors; seminars/workshops carried out by researchers/professors from research centers of excellence (national and international) and with curricular experience in different areas under analysis and emphasizing simulations and discussions in the design of new molecules based on the structure of biomolecules deposited in the bases of international data. Students will be evaluated via: 1- the performance of an individual work (60% TP final grade) focusing on the experimental and computational approaches taught to determine the structure and dynamics of macromolecules of biological systems with an emphasis on clinically relevant problems ; 2- test of knowledge acquired in the three taught modules (contribution of 40% TP final grade).
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Language |
Portuguese. Tutorial support is available in English.
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