Structural and Computational Biology

Proteins are essential components of all living cells. The determination of their structures at a molecular level gives us a better picture of how
they work both in physiological and pathological states. The combination of structural and functional studies is the most rewarding route to an understanding of the molecular basis of biological function. Computational biology is essential to integrate the variety of tools and heterogeneous data into a comprehensive
spatial and temporal description of biological processes. The course will analyze the basic aspects of structural and computational biology.

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Basics of molecular structures: proteins, DNA, sugars.
• Basics of structural bioinformatics: sequence alignment, sequence/structure alignment, motif search, domain prediction (e.g. alphafold). Protein Data Bank.
• Basics of protein production: cloning, expression and purification.
• Basics of structure determination: X-ray crystallography, SAXS, NMR, CD, MD, cryo-EM.
• Structural basis of DNA replication, repair and aging.
• Structural basis of immunity: antibodies, antibody/antigen interactions, inflammasome.
• Structural basis of viral infection: cryo- EM structure of viruses, viral proteins.

The course focus on the contribute of Structural and Computational Biology to the understanding of the basic molecular processes. Students will learn what are the main experimental and computational techniques used to get a molecular structure both from theoretical (lectures) and practical (tutorials) point of views. To stimulate their interest the structural basis of the main cellular processes will be reviewed and discussed in journal club sessions.

Written exam - 30%
Final seminar - 70%

Matteo De March is assistant professor in the field of molecular biology and biochemistry at the University of Nova Gorica. His main research interests focus on the structure and function of biomedically relevant proteins, such as chromatin remodellers critical for genome maintainance, antibody-receptor complexes in immunity and host-defence antiviral systems.
1. C-terminal domain of the human zinc transporter hznt8 is structurally indistinguishable from its disease risk variant (R325W). Ullah, R., Shehzad, A., Shah, M.A., ...Rahman, M., McPherson, M.J. International Journal of Molecular Sciences, 2020, 21(3), 926.
2. P15PAF binding to PCNA modulates the DNA sliding surface. De March, M., Barrera-Vilarmau, S., Crespan, E., ...Blanco, F.J., De Biasio, A. Nucleic Acids Research, 2018, 46(18), pp. 9816–9828.
3. The permeation mechanism of organic cations through a CNG mimic channel. Napolitano, L.M.R., Marchesi,
A., Rodriguez, A., ...Laio, A., Torre, V. PLoS Computational Biology, 2018, 14(8), e1006295.
4. The human RecQ4 helicase contains a functional RecQ C-terminal region (RQC) that is essential for activity. Mojumdar, A., De March, M., Marino, F., Onesti, S. Journal of Biological Chemistry, 2017, 292(10), pp. 4176–4184.
5. Structural basis of human PCNA sliding on DNA. De March, M., Merino, N., Barrera-Vilarmau, S., ...Blanco, F.J., De Biasio, A. Nature Communications, 2017, 8, 13935.