Lecture 2 Flashcards
What is divergent evolution?
Starts from common ancestor and diverge
What is convergent evolution
No common ancestor become more similar
What causes functional similarity?
not sequence similarity or functional similarity it is the fact that they are ralated through divergent evolution
How can you detect homology?
sequence based, structure based or position based
When are two sequences homologous
Alignment used: alignment similarity of above 25%
Which alignment values are useful?
Raw result: Not useful for similarity just gives best alignment
E-value: useful for judging significance of homology
p-value: nearly identical to E-value
What is evolutionary correspondence?
Corresponding residues are derived from a common precursor of the ancestral gene
What is structural correspondence?
corresponding residues occupy analogous positions in the 3D structure
What is functional correspondence?
corresponding residues fullfill the same role in both proteins
Why are proteins better conserved than DNA?
Genetic code degeneracy
AA similarity / exchange frequency
How to predict a teritary structure?
Homolgy modelling (look at known structures and sequences and compare to new sequence), Fold recognition (comparison to many candidate templates and judged by structural aspects)
What is to be considered in machine learning datasets?
Training, Validation, Testing dataset. Training must be sufficiently diverese to avoid overfitting and out of scope cases.
How can you determine the structure of a protein experimentally?
X-Ray cristallography, Alphafold, NRM (Nuclear Magnetic resonance), Cryo EM
What is a downside of X-ray cristallography?
Frozen snapshot -> no flexible regions visible
What are coiled coil regions
long amphipathic helics with heptad repeat pattern
What is 3.6 aa
One helix turn (One heptad repeat is 7 aa) slightly less than 2 turns
What are domains and why are they important?
often carriers of unit functionality (functional domains)
protein function can be deduced from domain function
Often subject to independent evolution
What is neo-functionalization?
often consequence of gene duplication can be mild or drastic
How to define a new motif?
Data: experimental indentification of relevant proteins (ER-targeting) + AA frequencies
Step 1: AA groups with high information content
Step 2: Calculate enrichment factor + significance
How to calculate the enrichment factor
In a group of 100 lumenal ER proteins, 20 contain the motif K-D-E-L>
The proteome comprises 25000 proteins, of which 200 contain K-D-E-L>
Enrichment factor = (20 * 24720) / (80 * 180)
What is hydrophobicity in aqueous solution
hydrophobic core more hydrophobic than exposed residues
What is hydrophobicity in lipid solution
hydrophobic core less hydrophobic than exposed residues
How do you predict a transmembrane protein?
Classification of AA by hydrophobicity scale
Evaluation of all possible windows by averaged hydrophobicity
How do you predict an amphipathic helix
periodicity of 3.6aa -> angle of 100° between consecutive residues (helical wheel diagram)
