Thursday, March 23, 2017

Unfolding ubiquitin: what breaks when?

The off-diagonal parts of the contact map contain all the non-trivial information of the folding. Therefore, if the protein unfolds (or we unfold it ourselves), all the off-diagonal parts will disappear. These animations can be fun to look at:

Or we can look at the unfolding, the force profile, and the contact maps together:

Animations are always really useful, but if we want to classify trajectories, or have a quick overview, it is better to summarize all the frames in one plot. ConAn has several time-encoded contact maps, for example, on the total interaction time:

This shows that there are roughly speaking three groups of contact losses:

  1. Around ~15-25%: residues 0-10 losing contact with 10-20 and 60-70.
  2. Around ~40%: residues 25-70 losing contact with each other.
  3. Around ~70%: residues 20-40 losing helicity.
We can also encode the initial secondary structure to easier interpret this plot (ubiquitin is formed of an helix and four beta strands):

Another option is a time-encoded plot of last encounters:

The contacts are more widespread in this case as short-lived intermediates form residues 25-70 appear.

In case you are studying folding instead (or non-native intermediates during unfolding), you will also find the opposite plot interesting, i.e., time of the first encounter:

Strand β4 forms a short-lived helical intermediate around 150 ns.

If we had several different trajectories, any of these 3 statistics (although probably the total interaction time would be the best) could be a good basis for clustering them, either "by eye" or by some more sophisticated method.

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