Research area
Keeping enzymes working outside water
Doctoral work on random copolymers as synthetic chaperones for enzymes in water-miscible organic solvents, screened on an automated plate-based platform.
Enzymes are extraordinary catalysts in water and frequently useless outside it. Move one into a water-miscible organic solvent, often where the interesting synthetic chemistry happens, and it tends to unfold, aggregate and drop out of solution.
Random copolymers can act as synthetic chaperones, wrapping a protein in a shell whose chemistry is tunable monomer by monomer. The difficulty is that the relationship between that shell's composition and whether the enzyme survives is not obvious from first principles.
The space is too big to reason about
Why this has to be run in parallel
A deliberately conservative design space: six monomers, three per polymer, composition in 10% steps, four chain lengths, and it is already past what anyone screens by hand.
2,880 polymers is about 30 plates. At one hand-run reaction per hour it is years of benchwork; on an automated platform it is a manageable campaign. And the real space is larger, because composition does not come in tidy 10% steps.
Show the numbers
| Quantity | Value | How |
|---|---|---|
| Monomers available | 6 | an illustrative palette |
| Monomers per copolymer | 3 | terpolymers |
| Distinct monomer sets | 20 | C(6,3) |
| Compositions per set | 36 | 10% increments summing to 100% |
| Chain-length targets | 4 | degree of polymerisation |
| Total distinct polymers | 2,880 | 20 × 36 × 4 |
| Plates required | 30 | at 96 formulations per plate |
Computed Plain combinatorial arithmetic for an illustrative palette, not a description of a specific screen. The point is the order of magnitude.
How the screen runs
The assay, end to end
Each step has to survive being done ninety-six times in parallel without the numbers drifting.
Show the numbers
| Step | Stage | Detail |
|---|---|---|
| 1 | Synthesise copolymer library | photo-ATRP, one plate |
| 2 | Add enzyme | form polymer–enzyme hybrid |
| 3 | Transfer to organic solvent | water-miscible |
| 4 | Read solubility | plate reader |
| 5 | Read retained activity | enzyme assay |
| 6 | Model structure–function | on every well, including failures |
Schematic A diagram of the approach. Results from this work are in preparation and are not shown here.
Two things make this work as a dataset rather than a set of experiments. Every well is measured the same way, and the wells that fail are kept. A polymer that leaves the enzyme insoluble produces a number, and that number is as informative for modelling as a success.
This work is in preparation. No results are shown on this page, and the figures above describe the approach rather than reporting outcomes.
Status
This is ongoing doctoral work and the manuscript is in preparation. If you are working on something adjacent, I would rather talk before it is published than after.