Task 6 - EVfold

For the proteins used in this practical, structures have been determined. However, in real-life projects, you often do not have protein structures only sequences. During this practical, you already predicted secondary structure elements

correlated mutations

calculating the evolutionary couplings

0. aligment (clustalw.... Pfam alignment good)

1. a2m2lm.... => aligment 2. freecontact -> standard (installed on student computers)

Output -> all couplings + evolutionary coupling score (last column)

rank by score => look at distrubution, values, range

Meaning of score unclear

Take only scores for i+6, i.e. neighboring residues neglected, minimal 5 residues between coupled residues

Take ranking, check for each coupled pair the actual distance in the structure. TP: distance <= 5 AA (minimal distance of all pairs of all atoms of both residues)

EVcoupling Check evolutionary hot spots, i.e. relevant residues, functionally important sites. Take L couplings (L=length of protein sequence), sum scores for each residue. Analyze. (Cell paper)

- compare to conservation, single site conservation

EVfold.org