01
Sequence & Diversity
Metagenomes, homologues, ancestral reconstruction and scaffold discovery to expand beyond familiar enzyme families.
Protein engineering • biocatalysis • computational design
Explore the protein design space.
A scientific webspace for mapping sequence diversity, engineering enzymes, analysing patent landscapes and translating protein designs into robust biocatalysts.
PDS
Core themes
Where design meets industrial biology
The site is structured around the full path from biological diversity to engineered function, process performance and commercial relevance.
02
Protein Engineering
Directed evolution, rational design, structure-guided libraries, second-shell residues, tunnels, interfaces and stability engineering.
03
AI-Assisted Design
Protein language models, structure prediction, generative sequence design and active-learning loops for faster search of high-dimensional sequence space.
04
Biocatalysis
Enzyme selectivity, substrate loading, solvent tolerance, cofactor economy, immobilisation, reuse and scalable reaction engineering.
05
Patent Intelligence
Map sequence claims, mutation hotspots, process claims, expiry, legal status and potential design-around or white-space opportunities.
06
TEA & LCA
Connect enzyme performance to cost, waste, E-factor, energy, productivity and long-term environmental performance.
Design workflow
A practical protein-design pipeline
A reusable framework for discovering and developing enzymes for new substrates and greener synthesis.
1. Map biologyGenome, metagenome, family diversity, phylogeny and functional annotation.
2. Map IPSequence claims, mutation positions, process claims, assignees and expiry.
3. Design librariesStructure, docking, tunnels, dynamics, language models and active-learning selection.
4. Validate functionExpression, activity, selectivity, solvent/stability profiles and substrate loading.
5. TranslateImmobilisation, recycling, process integration, TEA, LCA and manufacturing readiness.
Focus area
Transaminases & sitagliptin
Sitagliptin is a useful industrial case study for how enzyme engineering moves from difficult substrate recognition to high-selectivity manufacturing, and then into immobilisation, catalyst reuse, cofactor economy and new sequence families.
- Historical evolution of engineered ω-transaminases
- Patent families and sequence-space constraints
- Immobilised and reusable catalyst architectures
- New scaffolds from metagenomic and fungal diversity
- Future engineering positions beyond known hotspots
Patent landscape
Claim-aware design space
The objective is not merely to catalogue patents, but to translate patent claims into experimentally meaningful design questions.
- Which sequence families are heavily claimed?
- Which residues repeatedly appear in engineered claims?
- Which structural regions remain underexplored?
- Which immobilisation and cofactor strategies are crowded?
- Where can novel biology create genuinely distinct solutions?
Future design space
Beyond the obvious mutations
The most valuable future work may come from combining new biological diversity with modern computational tools and manufacturing-aware selection criteria.
Metagenome mining
Search uncultured diversity for transaminase scaffolds with novel active-site geometry, stability and solvent tolerance.
Structure-aware white space
Project patent mutation positions onto 3D structures to identify underexplored loops, tunnels, second-shell networks and oligomer interfaces.
Generative protein design
Use protein language models and structure-conditioned generation to propose sequences outside familiar natural neighbourhoods.
Active learning
Close the design-build-test-learn loop by selecting variants that maximise information gain as well as catalytic performance.
Whole-system optimisation
Co-optimise enzyme, amino donor, PLP level, immobilisation, solvent and downstream isolation instead of treating them as separate problems.
TEA/LCA-guided engineering
Prioritise variants that improve process economics and environmental metrics, not merely assay activity.
About this webspace
Protein Design Space
An independent scientific platform for exploring protein engineering, enzyme discovery, industrial biocatalysis and patent-informed innovation. The site can later be expanded with review articles, interactive patent maps, mutation visualisations, downloadable datasets and project notes.
Independent Researcher · New South Wales, Australia