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.

5-hydroxytryptophan biosynthesis

 

I was intrigued by a recent article in the journal Chem (link)  entitled "Creation of Bacterial Cells with 5-hydroxytryptophan as a 21st Amino Acid Building Block" by Chen et al. in the group of Han Xiao at Rice University, wherein they make a strain that metabolically produces 5-hydroxytryptophan for genetic code expansion. It is an interesting example of why metabolic engineering is non-trivial and how scientific research does not progress in a logical fashion.

Switching ligand in a PDB with Fragmenstein

For the Covid Moonshot project, one question by Prof. Frank von Delft of Diamond XChem led to a series of events that culminated in Fragmenstein, a module to do fragment mergers when the followup is as faithful to the starting crystal hits as possible. Even if it's intended use is the hit-to-lead process, there is a nice use that make it rather handy for computational biochemistry in general: switching the ligand in a PDB to another in an energy minimised fashion that obeys the original ligand.

Atom names purely in RDKit

For some applications, such as PyMOL scripts or Rosetta, atom names are really important, say CA is the standard name for the α-carbon. Example uses of atom names in Rosetta/pyrosetta include setting constraints, using a params file for a custom ligand and so forth. However, RDKit is a bit of a nuisance with atom names as it is not a central feature, but a feature added for PDB files that is not too well documented.

What-if: Biosynthesis of deazaguanine

7-deazaguanine is an analogue of guanine that has a carbon instead of a nitrogen. This molecule that is not made in nature, but many substituted versions, namely queine, archaeosine nucleobase and their precursors. These are made via a different route. However, it would be very feasible to make via straightforward enzymology.

Go away glycerol!!

Due to the nature of crystallisation additives are often found in PDB structures. These are generally unwelcome, especially if you want to extract ligands. In fact, I have heard only once someone talk excitedly about their crystallisation reagent in their structure, but only because they were trying to flog it off as an allosteric binding site. Generally, they are just annoying. Luckily you don't need reinvent the wheel as a list or two already exist!

RDKit for Rosetta: PLP ligand space as an example

Docking requires a molecule to dock. Preparing a ligand is often tricky, especially if the ligand is complicated, such as PLP. PLP is an interesting cofactor as it catalyses the reaction while the protein chooses the ligand. It binds tightly to the active site via its phosphate and its pyridine ring, while the metabolite to be transformed forms a Schiff base with it. Therefore, one would think that it makes easy to explore chemistry space with it. However, several technical hurdles are encountered, making it quite didactic.

The secondary metabolism of pineberry strawberries

For an upcoming open-day we will extract DNA from strawberries. For this I made a slide that explains how DNA mutations lead to protein variants, than in turn lead to different phenotypes (redness in the strawberry's case). In doing this, I got fascinated by a strawberry cultivar called "Pineberry". But not because it is unpigmented, but because the reviews online say it is bland, which means that a rather early enzyme is missing resulting in a unpigmented phenotype and a bland phenotype.

The curious case of fluorescein and implicit waters

I recently was asked a straightforward task: get the energy scores of a given protein by itself, conjugated with fluorescein maleimide and its ring opened form. Despite that, I failed miserably because of implicit waters playing odd tricks.
Given that it is of no real use, I am happy to share so to give a tutorial of how to do that in Rosetta (ligand docking), which I found taxing the first time.