## Proteins in bioinformatics

- Introduction to my classes  
- Differences between Bioinformatics and Computational Biology  
- AI from Deep Blue to AlphaFold  
- The protein folding problem  

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### Protein coding genes in genomic sequences and annotation of proteins

- DNA, proteins: length scale  
  - Protein length  
  - Protein mass  
- Bioinformatics works with life, humans and computers  
- Storing information:  
  - strings of bits (computers)  
  - DNA sequences  
  - protein sequences  
  - applications in biology:  
    - a DNA storage device  
- FASTA file format, MultiFASTA file format  
- UniProt  
- UCSC Genome Browser  
- BLAT  
- Three simple tasks:  
  - taxonomy ID / Lineage (NCBI/UniProt)  
  - spike glycoprotein (SARS-CoV-2): see it in its reference genome  
  - compare the sequence (SARS and SARS-CoV-2) of a protein  
- How to (Python):  
  - protein length / proteome length  
  - amino acid mass  
  - proteome mass / average protein mass  

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### Homology

- Homology intro: homology, similarity, analogy (examples)  
- Protein: relation between sequence, structure and function  
- The Rost curve  
- Gene duplication, speciation  
- Paralogy (gene duplication), orthology (speciation)  
- Convergent evolution  
- Horizontal gene transfer  
- BLAST, BLASTP  
- First protein sequence against a database search (Russell F. Doolittle)  

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### Multiple sequence alignment (MSA)

- Introduction to alignment  
- Classical alignment representation: `*` (identity), `:` (conserved), `.` (semi-conserved), blank ` ` (mismatch)  
- An application of sequence alignment to epigenetics: bisulphite sequencing  
- Introduction to sequence alignment  
- Pairwise alignment vs. multiple sequence alignment: why is it good to perform an MSA?  
- Pairwise alignment: a brute-force algorithm  
- Basic metrics: Hamming, Levenshtein  
- Scoring schemes, substitution matrices (Dayhoff PAM, BLOSUM)  
- Gaps (indels)  
- Classification of algorithms: global alignments (Needleman–Wunsch) vs. local alignments (Smith–Waterman)  
- Multiple alignment implies pairwise alignment  
- Pairwise alignment does not imply multiple alignment  
- Pairwise alignment: different methods and applications  
- Dynamic programming: from the Manhattan graph problem to sequence alignment  
  - Combinatorial optimization:  
    - Seven bridges of Königsberg (graphs)  
    - Travelling Salesman Problem (TSP)  
    - Manhattan tourist problem  
- Dynamic programming computational complexity and the necessity of using heuristics. What is a heuristic?  
- Word methods for pairwise alignment: BLAST, FASTA  
- Sequence alignment profiles, sequence logos  
- Can we align a profile against a sequence? Can we align a profile against a profile?  
- Multiple sequence alignment: the algorithm  

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### Phylogeny

- Taxonomy, evolution and phylogeny: definitions  
- Homology, similarity, clustering and hierarchical clustering  
- Phylogenetic tree (data structure)  
- Phylogenetic trees (unrooted and rooted, examples)  
- Earlier phylogenetic studies from the molecular evolution perspective:  
  - phylogenetic study on fishes (Reichert and Brown 1909)  
  - divergence between chimp and humans  
  - the 3rd kingdom of life: Archaea (Woese)  
  - modern mitochondrial DNA in forensic studies  
- What is a tree? (from graphs)  
- Building phylogenetic trees: phenetic and cladistic approach  
- UPGMA method  
- Maximum parsimony method  
- Varying rates of evolution (lizards, crocodiles and birds)  
- TimeTree: the timescale of life  

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### Protein structure

- Central dogma of Molecular Biology  
- Amino acids, polypeptides  
- Chemical properties of the amino acids, classification  
- Protein structure (different chemical interactions, dissociation energies)  
- Protein structure: primary, secondary, tertiary, quaternary structures  
- Protein folding problem:  
  1. Levinthal's paradox  
  2. Anfinsen's dogma  
- Relation between protein sequence, structure and function  

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### PDB (Protein Data Bank)

- Intro to the Data Bank  
- Evolution of the database  
- Current state, different experimental method contributions  
- Computed structural models (AlphaFold)  
- X-ray crystallography  
- Nuclear magnetic resonance  
- Electron microscopy  
- RCSB PDB: what can I retrieve from a PDB ID?  
- PDB text file description  
- Graphical tools for visualisation: Chimera