Computational Molecular Biology (Elective)

Sandipan Mohanty (Forschungzentrum Jülich), Giulia Rossetti, Emiliano Ippoliti, Jens Dreyer 

Scope of the course: To provide a molecular basis of life processes for students who are willing to use informatics and calculus.

Programme

Part A - STRUCTURAL BIOLOGY
- Structure of cytoplasmatic  and membrane proteins. Structure of the nucleic acids.
- Disordered proteins
- Thermodynamic basis of the stability of folded biomolecular structure
- Thermodynamics of protein/ligand interactions
- Computer-aided drug design
- Physical basis of protein function, metabolism and cytoskeleton.
- Molecular basis of human perception. - HIV-1 attack of human cell: a molecular perspective
- Protein assembly (protein-protein complexes, protein-protein interactions in protein dimers, crystals and virus capsids)

Exercise:
- Presentation by each student regarding structure and function of a protein.

Part B - STRUCTURAL BIOINFORMATICS
- Evolutionary processes and phylogenetic trees
- Sequence searching: pattern matching and BLAST
- Sequence alignment
- Principles of Information Theory and Thermodynamics
- Secondary structure assignment and prediction
- Tertiary structure: from random coil to stable fold
- Tertiary structure prediction and modeling
- Protein Interactions: complexes and networks
- Genome analysis and comparison
- Programming guidelines and algorithms

Exercises:
- Homology modeling (including BLAST, multiple alignment, target selection, model evaluation)
- Data analysis with R (principles of R, benchmarking (ROCR), structure analysis (BIO3D))

Part C - MOLECULAR MODELING
- Basic elements of molecular modeling
- Electrostatic modeling
- Energy minimization based on force fields
- Molecular dynamics
- Molecular modeling

Exercises:
- Setting up and running of an MD simulation of a small tripeptide in vacuum and in aqueous solution by using the open source NAMD and Gromacs codes
- Conformational analysis
- MD-based structural predictions in molecular medicine: high-throughput analysis of all of prion-diseases linked mutations involving the prion’s globular domain

Literature:

1. A. Lesk: Introduction to Bioinformatics (2002)
2. A. V. Finkelstein and O. B. Ptitsyn: Protein Physics (2002)
3. A. Leach: Molecular Modeling: Principles and Applications (2001)
4. C. Branden and J. Tooze: Introduction to Protein Structure (1999)
5. A. Fersht: Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding (1998)