Summary Computational Biology

Lectures
Building blocks of life
Molecular biology primer (from gene to protein)
Central dogma molecular biology




 mRNA longer & heavier
 Proteins synthesized in cytoplasm



Proteins more abundant, why study DNA?

 DNA (&RNA) sequencing can be automated



Seq technologies

 1st generation: Sanger seq
- Short read
- Infer nucleotide identity using dNTPs
- Visualize with electrophoresis
 2nd gen (NGS): Illumina
- Short read
- High throughput from parallelization of seq reactions
 3rd gen: Oxford Nanopore
- Long read
- Seq native DNA in real time with single molecule resolution



Longer read length  higher error

 Combine long & short read tech to cover gaps & correct seq errors



Genome => full set of chromosomes or genes in a gamete of diploid organism

 Regular somatic cell contains 2 full sets of genomes (& mtDNA)
 Haploid organisms: cell contains 1 set of genome
 Mt & chloroplast genome: also 1 set

,Size of genomes: does not correlate with complexity




Gene => DNA based unit that can exert its effect on organism through RNA or
protein products

 1 gene  1 protein
 Programmable unit that can give rise to multitude of products: proteins &
RNA products through splicing



Translation

1. Initiation
2. Elongation
3. Termination



Bioinformatics = gene encoded in 1 strand + scan model takes 1 st ATG as start
codon

 ORF finding program



Reading frame => way of dividing seq of nucleotides in DNA or RNA molecule
into a set of consecutive, non-overlapping triplets



Open reading frame (ORF) => spans of DNA seq between start & stop codons

,Amino acids
Why study aa?

 20 aa
 Lock & key property
 Serine proteases
- Chymotrypsin cuts after Phe, Trp & Tyr
- Trypsin cuts after Lys & Arg
- Elastase cuts after Ala, Gly & Val
Composition helps predict
- Protein structure
- Possible biochemical structure
- Protein functionality
- Mutability & evolution



Secondary structure

 Alpha helix
 Beta strand
 (beta) turn


Proteins

 Macromolecules made up from 20 aa
 Heart of aa = C alpha, bound to:
- Amino group (backbone)
- Carboxyl group (backbone)
- Hydrogen (backbone)
- Side chain R



Di-peptide

 Binding of aa to form protein: 2 protons from NH3 & 1 O from carboxyl
join  form water
 Peptide bond: C=O at one side & N-H at other side
- Only ends of chain are NH3 or carboxylic  charged



Amino acid sequence = primary structure

 Order of aa in protein chain
 Always read from N term to C term of protein
- N term = +H3N
- C term = COO-

, 20 aa




 Side chain (R) determines differences in structural & chemical properties
of 20 natural aa
 Several aa in >1 category
 Characterisation: multiple ways
- Hydrophobicity
- Size
- Charge
- Secondary structure preference
- Alcoholicity
- Aromaticity
- Special characteristics: bridge forming by cysteines, rigidity of prolines,
titrating at phys pH of histidine, flexibility of glycines



Amino acid characteristics
Glycine (G) & alanine (A)

 Small & neutral
 G (Gly)
- Smallest residue, hydrophobicity undetermined (no R)
- Turns 😊 no R  flexible backbone > strands 😐 > helix ☹
- No chiral center: <4 different groups bound to it, 2 protons on C alpha
 A (Ala)
- Small hydrophobic residue
- R = methyl group
- Alpha helix 😊 > beta strands 😐 > beta turns ☹
- Subset of all other aa