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.

Per residue RMSD

Recently I calculated the local RMSD caused by each residue and I thought I'd share the methods I used using PyRosetta —it is nothing at all novel, but I could not find a suitable implementation. The task is simple given two poses, find out what residue's backbone is changing the most by scanning along comparing each a short peptide window from each.

Remodel in Pyrosetta

The Rosetta binary Remodel is a great tool as it allows interesting designs to be made. However, it is rather incompatible with Rosetta Scripts and Pyrosetta as it is heavily dependent on command line options for customisation and repeats some of the processes internally. Despite this, it can be cohersed rather effectively to work in Pyrosetta with some convenience and this is how.

Multiple poses in NGLView

As mentioned previously, most of my Pyrosetta operations are done in a Jupyter notebook run in a cluster node. As a result, I am heavily dependent on NGLView, an IPython widget that uses NGL.js. This is nice for some quick tasks, although admitted more limited than the PyMOL mover, which however requires another ssh to forward another port. My Michelanglo webapp uses NGL.js, so I cannot but say good things of NGL.js. However, one or two things in the Python module NGLView are not immediately clear, so I'll quickly cover dealing with multiple poses here.

Things I wish I had known about Raspberry Pis

Raspberry Pis are very fun to play with and are relatively cheap —I believe I have 6 or 7 Pis running across the house. However, very often I learnt a thing or two that I wish I had known beforehand —sometimes rather fortuitously. So here is my list of top "in-hindsight" tips from the perspective of a seasoned coder with no prior electronics experience.

From cartoon to interactive infographic –the sane way

Making cartoon representations (technically vector graphics) in Adobe Illustrator is very fun, whereas the very idea of making a cartoon representation via line plots with Excel, Matlab, R, Plotly etc. would make anyone insane even just thinking about it. Luckily Illustrator images can be coloured based on numerical data in an automated way... without being manually plotted in Excel. Here I discuss exporting the vector graphic and modifying it with D3.js in a Jupyter notebook.