Show neighbours in nglview

Nglview is a really nice Python library which encodes a widget to show a NGL viewport, a JS 3D protein viewer used until recently by the PDB. One annoying feature is that one cannot select neighbours as easily as say PyMOL's "select byres HEM around 3".  But it is possible and here is how.

JS in Colab

A Jupyter or Colab notebook has two sides, one is the Python kernel, which may be running on a remote machine, and the front-end running in one's browser. The JavaScript in the browser and the Python kernel as a result may be on separate machine, yet it is possible to make them dialogue. However, this differs between Jupyter and Colab, the latter being more restrictive. I have found this difference problematic and even though I may not be fully versed in Colab functionality I want share some pointers, discussed below. Majorly:

• Colab diverges greatly from Jupyter in terms of JS operations.
• JS code injected into Colab is sandboxed within each cell.
• There is no requireJS in Colab cells or window.
• Imported modules have to be external to Colab/Drive.

Covalents, patches and N-O-S bridges in PyRosetta

Crosslinked residues are common, but for sure make up for it by being simultaneously highly intriguing and highly technically problematic. Oddly, I seem to keep bumping into them. During my PhD a decade ago I saw a talk by the father of Kiwi structural biochemistry, Ted Baker, about a curious case where they found an isopeptide bonds hidden in their crystal density. In a postdoc I worked with isopeptide bonds —I blogged about isopeptide bonds in Rosetta four years ago. During the start of the pandemic I dis some covalent-docking of compounds with PyRosetta for the Covid Moonshoot project, which evolved into Fragmenstein. Most tools have a hard time with crosslinks. And last month the Twittersphere was abuzz with the news of lysine-hydroxylcysteine (N-O-S) bridges in protein.

PyMOL will strip LINK entries from PDBs on saving while NGL obeys only CONECT entries in PBDs. An exception is PyRosetta: it behaves very nicely with disulfides, isopeptide bonds ( cf. repo of PyRosetta code from Keeble et al.) and other crosslinks —mostly. As a result I thought I'd add a note on how to add them in PyRosetta.

ggplot colours in Python

In my post about multiple poses in NGLView I mention using ggplot colours in Python, here I revisit it in a bit more detail. Warning: Contains colour theory which may befuddle some viewers.

Multiple sequence alignments

A sequence alignment is a rather important tool.

• Sequence conservation is a key ingredient in most nucleotide mutation severity predictors.
• The covariance within it powers the AlphaFold2 Evoformer and other de novo structure predictors.
• The phylogeny extracted from it tells the evolutionary tale of the protein

However, on the very basic level, i.e. getting a nice figure, far from the world of covariance matrices, it is a slight nuisance.

Therefore I would like share some pointers on choosing species and two python operation, namely getting the equivalent residue in a homologue and making a figure in Plotly. Just like with docking, where careful and diligent human choices make all the difference, rational choices help greatly with clarity for sequence alignments.

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.