## Proteins in bioinformatics

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### Protein coding genes in genomic sequences and annotation of proteins  
    -DNA, proteins: length scale  
        - Protein length
        - Protein weight
    -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  
    -BLAT  

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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 (MAS)  
   -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 good to perform a MAS?  
   -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 and Wunsch) vs. local alignments (Smith and Waterman)  
   -multiple alignment implies pairwise alignment.  
   -pairwise alignment does not implies multiple alignment.  
   -pairwise alignment, different methods and applications  
   -dynamic programming: from the manhattan graph problem to seq. 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 an 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
   -PAX6 exercise

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### Phylogeny
   -phylogenetic tree 
   -what is a tree? (as a graph)
   -building phylogenetic trees: phenetic and cladistic approach
   -UPGMA method (example)
   -time Tree: 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, dissociations energies)  
   -protein structure: primary, secondary, tertiary, quaternary structures.  
   -protein folding problem:   
       1. Levinthal's paradox  
       2. Anfinsen's dogma  
   -relation between: prot. sequence, prot. structure and prot. function

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### PDB (protein data bank)  
  -intro to the data Bank.  
  -evolution of the database  
  -current state, diff. 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