Move aside coIP Westerns, ColabFold has got this!

Recently AlphaFold2 released a new batch of models, this time covering all of the Trembl sequences in Uniprot, resulting in a huge number, which got hashtag-academic-twitter and some news editors very excited for the stamp-collecting feat. Personally, I find it annoying, not because it's pointless, but as of writing this, it has made any search for a target by name swamped by irrelevant sequences.
However, AlphaFold is great for other feats.
I have blogged about it a few times (e.g. link), which gives away my positive view of it! It can predict oligomers, with a lot more precision and confidence than docking. It does not always work either technically or meet the hypothesis. I did a long series of experiments with a hypothesis in mind which wasn't valid in the end (here), but revealed novel science and took a few minutes to set up and a few hours to run, which would have taken years if done by Western blot of a co-immunoprecipitation or cross-linking mass-spec.

Filling missing loops by cannibalising AlphaFold2

I could not resist this Photoshop.
But the process is not as dramatic
and the results not as bad as Temple of Doom...
If done right.

AlphaFold2 models have a complete sequence, but for innumerable reasons the crystal structure of the protein is better, but may have missing spans. As a result one may want, for illustrative purposes only, to rip out the required parts from the AlphaFold2 models (as fragments) and have them built into the target structure. Here is how to do it by threading.

Tweaking AlphaFold2 models with PyRosetta

In a previous post I explored the pitfalls of an AlphaFold2 model from EBI. Here I thought I'd share some PyRosetta methods that may be handy to use with AlphaFold2 models.

What to look out for with an AlphaFold2 model

There is nothing more disheartening than telling someone "Sorry, I cannot help you with your protein, because no homologue structures of your protein are solved and any model will be rubbish". Now, with AlphaFold2 proteome release this is no longer the case. Or mostly: in fact there are several pitfalls and issues that need to be looked at, because the algorithm does not account for three things: binding partners and ligands, oligomerisation and alternate conformations.