Bi4999en – Structural Biology and Bioinformatics


Academic term: Autumn 2023


Course content:

1.      Introduction to the structure of macromolecules – composition, methods for determination,
application in biology, visualization.

2.      Structure of biomolecules – different levels of structure of proteins and nucleic acids

3.      Bioinformatics databases and structure prediction – sequence databases, structural
databases, retrieval and evaluation of macromolecular structures

4.      Structural databases and models of structures – structural databases, validation and
methods for quality assessment, preparation of models.

5.      Stability and dynamics of macromolecules – analysis of molecular dynamics and stability,
prediction of stability, databases.

6.      Analysis of protein structures – identification of important regions: binding/active sites,
aggregation propensity, transport pathways, flexible regions, binding/catalytic amino acids.

7.      Protein-ligand complexes – evaluation of complexes, analysis of interactions, druggability,
databases, transport of small molecules.

8.      Macromolecular complexes and interactions – protein-protein and protein-DNA complexes,
analysis of interactions, databases.

9.      Engineering of protein structures – effect of mutations on the protein structure, stability
and function.

10.  Applications of structural biology and bioinformatics – biological research, drug design,
engineering of biocatalysts.


Detailed content

1. Introduction to the structure of macromolecules

·         Course information

·         Other courses from LL

·         Motivation and applications of structural biology

·         Structural biology: basics and historical perspective

·         Structure visualization

·         Energetics and molecular interactions

·         Experimental methods for structure determination

·         Basics of Bioinformatics: sequence, databases, homology modelling, machine learning, ab
initio

2. Structure of biomolecules

·         Proteins: primary to quaternary structures

·         Calculation of secondary structures: DSSP method

·         Protein motifs, domains and folds

·         Nucleic acids: primary to higher structures

·         Structural data formats: types of data format; PDB, mmCIF and PDBML

·         Structural databases (list)

3. Bioinformatics databases and structure prediction

·         Sequence-structure-function relationship (intro) [or refer to 1-4ry structures
progression]

·         Sequence databases

·         Sequence alignments

·         Sequence analysis (prediction of properties at sequence level (eg. solubility)

·         Sequence-structure-function relationship

·         Structure prediction from sequence

4. Structural databases and models of structures

·         Structural databases

·         Validation and quality assessment

5. Stability and dynamics of macromolecules

·         Protein folding

·         Protein stability, its prediction, databases

·         Protein dynamics

6. Analysis of protein structures

·         Solvent accessibility

·         Solubility and aggregation

·         Molecular interactions

·         Functional sites

·         Binding/catalytic amino acids

·         Evolutionary conservation

·         Transport pathways

7. Protein-ligand complexes

·         Structure of complexes

·         Databases of complexes

·         Protein druggability

·         Databases of small molecules

·         Molecular docking

·         Evaluation of complexes

·         Transport of small molecules

8. Macromolecular complexes and interactions

·         Evaluation of protein-protein and protein-DNA complexes

·         Analysis of protein-protein interactions

·         Databases

9. Engineering of protein structures

·         Types of mutations

·         Databases of mutations

·         Effects of mutation on protein structure and function

·         Prediction of mutation effects

10. Applications of structural biology and bioinformatics

·         Biological research

·         Drug design and development

·         Design of biocatalysts


Literature

·         J. Gu & P. E. Bourne (2009), Structural Bioinformatics, Wiley-Blackwell,

·         G. A. Petsko & D. Ringe (2004), Protein Structure and Function, New Science Press

·         Claverie, J-M., & Notredame, C. (2006), Bioinformatics for Dummies (2nd ed.) Wiley
Publishing, Hoboken, p. 436

·         Xiong, J. (2006) Essential Bioinformatics, Cambridge University Press, New York, p. 352.

·         T. Schwede & M. C. Peitsch (2008), Computational Structural Biology: Methods and
Applications, World Scientific Publishing Company

·         A. Liljas, L. Liljas, J. Piskur, G. Lindblom, P. Nissen, M. Kjeldgaard (2009), Textbook
Of Structural Biology, World Scientific Publishing Company


Evaluation methods

Multiple-choice test, multiple correct answers possible, 10 correct answers out of 25 needed to
pass the exam


Evaluation grading

Grades are based on the number of correct answers as follows:

A: 22-25

B: 19-21

C: 16-18

D: 13-15

E: 10-12

F (fail): < 10