PF Proteaform
Proteaform — Computational enzyme design

Enzymes designed, not discovered.

Most industrial reactions have no natural enzyme to borrow. We generate catalysts for them from scratch — so steps that need palladium, chlorinated solvents and cryogenic reactors can run in water, at room temperature.

PF-1 · designed backbone
78 residues · 3 helices · 2 strands

01 — The bottleneck

Chemistry built for refineries, used to make medicine.

A modern small-molecule drug takes eight to twelve synthetic steps. Most of them still run on chemistry inherited from petroleum processing: precious-metal catalysts, halogenated solvents, sub-zero reactors, and a waste stream twenty to a hundred times the mass of the product.

Enzymes do the same transformations at ambient temperature, in water, with the stereochemistry right the first time — when one happens to exist. For most reactions a process chemist actually needs, none does. The industry's answer has been to screen natural diversity for a distant relative and then evolve it: eighteen to thirty months of mutagenesis to reach a catalyst that survives a manufacturing plant, and no guarantee of a starting point at all.

We think that is a design problem wearing a search problem's clothes. Given the transition state you want stabilised, the active site that stabilises it can be generated — and the protein that holds it in place can be generated around it.

02 — Platform

PF-1, and the loop that keeps making it better.

PF-1 is a sequence–structure diffusion model conditioned on reaction geometry rather than on a homologous protein family. It is trained on public structural data and on our own paired library of variants and measured kinetics — the part that cannot be downloaded. Every campaign runs the same four stages, and every campaign ends by feeding the model.

01 / Design

Generate

PF-1 proposes active-site geometries around the target transition state, then builds a backbone that holds them. Roughly 105 candidate sequences per campaign, none of them derived from a natural homologue.

02 / Rank

Filter in silico

Folding, docking and stability models score every candidate for expressibility, melting temperature and predicted transition-state binding. Around a thousand survive to the bench — the step that makes the wet lab affordable.

03 / Build

Express

Genes are synthesised and expressed in E. coli, arrayed in 384-well plates. Cell-free expression runs alongside it for the designs we want an answer on this week rather than next month.

04 / Test

Measure

Kinetics by LC–MS on every variant, on the real substrate, under conditions a plant would use. Failures are measured with the same care as hits, because they carry as much signal.

Every measurement returns to training. Each campaign shortens the next.

03 — Where we are

Numbers from the first eighteen months.

14
Weeks, median, from target reaction to a catalyst that holds up at scale. Directed evolution takes 18–30 months.
2.1M
Variants in our internal training set with kinetics measured in-house, not inferred.
41×
Median gain in kcat/KM over the best natural starting point we could find for the same reaction.
68%
Lower process mass intensity than the incumbent chemical route on our lead program.
04 — Pipeline

Five programs, one platform.

Reaction classes chosen for how often they appear in routes that process chemists would rather not run.

Program Reaction class Sponsor Stage
PF-201 Stereoselective C–N coupling Undisclosed pharma partner Scale-up · 100 L
PF-118 Ketone → chiral amine (transaminase) Internal Lead optimisation
PF-095 Late-stage C–H hydroxylation Internal Lead optimisation
PF-233 Nitrile hydrolysis, non-natural substrate Internal Discovery
PF-260 Macrocyclisation Internal Discovery
05 — Compute

The wet lab is the slow part. Nothing else should be.

A campaign is worth running only if the design and ranking stages finish faster than the plates come back. That makes infrastructure a scientific constraint, not an IT one.

06 — Contact

If you run a route you wish you didn't, tell us about it.

We take on a small number of partnered programs a year, alongside our internal pipeline. We are also hiring scientists and engineers who want to work where the model meets the plate.