- 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
A segfault and NaN driven series of disconnected ideas, analyses and just plain silly posts about computational biochemistry, synthetic biology and microbiology.
Sunday 31 October 2021
Multiple sequence alignments
Sunday 17 October 2021
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. |
Monday 23 August 2021
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.
Tuesday 27 July 2021
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.
Wednesday 7 July 2021
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.
Monday 26 April 2021
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.
Monday 22 February 2021
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.