This subject attempts to apply knowledge at the molecular level in the treatment of various pathologies. To this end, various experimental methods are analyzed depending on the degree of knowledge of the molecules involved in these pathologies, with special emphasis on those in which structural details of the targets are known.

The subject is divided into two modules. In the first of them, the concepts of protein stability and folding and their relationship with pathological processes are developed. Also the cellular response to potentially pathological situations and the possible applicable therapies. In the second, the interactions between different macromolecules are systematically treated: proteins, nucleic acids and lipids. The types of interactions that allow the formation of stable complexes between them and the regulation of their relative affinity are described. In the protein-ligand interaction topic block, basic concepts of the design and optimization of protein inhibitors are described. As it is a subject that is taught in the second semester of the last year of the degree, it will use the general knowledge acquired by the student (protein structure, metabolism, thermodynamics, etc.). An attempt will be made to integrate this knowledge to give it an applied projection.



Contents

Conformational stability of proteins. Protein folding. Pathologies related to protein folding. Protein-ligand interactions. Drug design. Protein-protein interactions. Protein-nucleic acid interactions. Protein-lipid interactions. Structural engineering. Design of protein functions.



Evaluation system

Master teaching will be evaluated through multiple-choice written tests and short questions (50-65%). Likewise, a monographic work will be carried out on a topic related to the subject, which will be presented in the seminars (10-15%). Activities related to computer practices will also be valued (20-25%)

Protein folding Native and denatured states. The denaturation balance. Thermodynamic stability of proteins. Measurement of conformational stability. Interactions that contribute to protein stability and relative importance. Importance of flexibility in protein functionality (intrinsically disordered proteins). Anfinsen experiment. Levinthal's paradox. The different stages of folding (intermediaries). Thermodynamic and kinetic aspects of folding. Transition and intermediary states. Implications of folding in different physiological and pathological processes.

Protein folding and pathology The problem of protein aggregation and chaperones. Intra and intermolecular chaperones. Pathologies related to defective protein folding: amyloidogenic diseases. Characteristics of the conformational transitions associated with these pathologies (prion, transthyretin,...). Cellular responses to protein misfolding and aggregation. Pharmacological chaperones. Current therapies and criticism of them.

Interactions between macromolecules Protein - ligand interactions. Drug design. Drug design. Design cycle. Rational and combinatorial design. Specificity, affinity and adaptability of a drug. Inhibitor optimization. Protein-protein interactions. Nature of interaction surfaces. Nature of interaction surfaces. Protein-lipid interactions. Structural engineering. ¿De novo¿ design of structures. Protein scaffolds: applications. Design of protein functions.

Theoretical classes, defense and criticism of research articles representative of the subject taught in groups of four students and computer practices.

• Final Assessment System
• Tools and qualification percentages:
  • Written test to be taken (%): 65
  • Realization of Practical Work (exercises, cases or problems) (%): 10
  • Team projects (problem solving, project design)) (%): 15
  • Exhibition of works, readings ... (%): 10

Evaluation system

Lecture teaching will be evaluated through multiple-choice written tests and short questions (80%). Likewise, a defense/criticism of a research work related to the subject matter will be carried out in groups of four people, with the participation of the entire group and the teacher (10%). Activities related to computer practices will also be valued (10%)

If the subject is not passed in the ordinary call, the partial grades of the well-rated sections will be saved for the extraordinary call of the current year (July).

NA

Basic bibliography

-Creighton, T.E. "Protein Structure. A practical Approach". IRL Press, 1990.

-Branden, C. and Tooze, J. "Introduction to protein structure". 2nd Edition. Garland Publishing, 1999.

-Creighton, T. E. "Proteins. Structures and molecular properties". W. H. Freeman & Co., 1994.

In-depth bibliography

-Fersht, A. "Structure and mechanism in protein chemistry". W.H. Freeman & Co., 1999.
-Lesk, A. M. "Introduction to protein architecture". Oxford University Press, 2000.
-Gómez-Moreno, C and Sancho J. (coords.) "Estructura de proteínas". Ariel Ciencia, 2003.

Journals

Revisiones sobre los temas tratados en la asignatura que se publiquen en revistas especializadas.

Web addresses

http://www.rcsb.org/pdb/

http://pdb-browsers.ebi.ac.uk/

http://ndbserver.rutgers.edu/NDB/

http://www.umass.edu/microbiol/rasmol

http://www.ebi.ac.uk/

http://www.expasy.ch/

http://www.ncbi.nlm.nih.gov/

http://cmm.info.nih.gov/modeling/
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http://www.csb.yale.edu
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