Task 6: Protein structure prediction from evolutionary sequence variation
Results
Contact Prediction
<figure id="ras_score_dist">
</figure>
<figtable id="hfe_score_dist" >
</figtable>
domain | length | reference | HS pairs | TP | FP | TP -rate |
---|---|---|---|---|---|---|
Ras | 160 | 5P21 | 65 | 53 | 12 | 0.82 |
MHC I | 174 | 1A6Z | 69 | 29 | 40 | 0.42 |
Ig C1-set | 76 | 1A6Z | 15 | 9 | 6 | 0.6 |
<figure id="cm_1a6z">
</figure> <figure id="cm_hras">
</figure>
- Why are the scores of residues close in sequence amongst the highest? Why are the pairs distant in sequence (n>5) more interesting for structure prediction?
It lies in the nature of proteins, that residues that are close in sequence, are also close in structure. Consequently, they are evolutionary coupled and show covariation in the multiple sequence alignment. The pairs that are at least five residues apart in sequence, are more interesting for structure prediction, because they contain more information about the overall topology of the protein, i.e. they reduce the space of possible protein conformations more than pairs that are close in sequence.
- Look at the values, range and distribution of scores.
For the MHC I domain of HFE_HUMAN, the score distribution is shown in table <xr id="hfe_score_dist" />. The values range from -0.94 to 2.57 with the mean at -0.07. The score distribution corresponds to a slightly right skewed normal distribution, where most values are in the range of -1 to 1. Only 0.5% of scores have a value above 1. Thus, scores with a value greater than one can be considered as high scoring.
- How many of the high-scoring pairs are true or false positives? Does this correlate with the value of the score? Visualize the predicted contacts together with the crystal structure contacts in a contact map plot.
As table <xr id="hs_table"> shows, the TP-rate among the high scoring pairs depends on the
- Can you determine evolutionary hot spots, i.e. functionally important residues? Compare to conserved sites in the MSA. Compare with your results from task 7 (when you are working on task 7, i.e. this is a task for the future).
- Here, the DI score is given. Compare the top 50 DI and CN (from freecontact) scores. How large is the overlap (>80%)?
MHC EVFOLD: constraints: 70(40%) 113(65%) 174(100%)
imm EVFOLD
RAS EVFOLD:
189 / 160
189:
76 (40%)
123 (65%)
189