Optimization starts with a candidate.
Protein optimization is a search across a vast functional sequence space. The signal is sparse, and the map is empty. You begin with one sequence — and a sense that there is something better, somewhere out there.
Somewhere out there is a better version.
Every mutation from the original candidate is a step into the unknown. Somewhere in that space sits a variant that is faster, more selective, more stable. The direction we have to travel is unknown, and often quite far.
Reality is not always kind.
Most mutations will result in either neutral or worse performance. In some cases, there is a valley of low-performing mutations separating our initial candidate from the best-performing variants.
How will we search?
There are many ways that people have done protein optimization. All of which have to make trade-offs based on the realities of preparing physical samples and running experiments.
Random Mutagenesis
Historical methods of directed evolution — DMS, SSM, error-prone PCR — are powerful tools for polishing an already good enzyme. They can generate a large number of candidates and leverage high-throughput screening technologies. However, because they stay so close to the original sequence, campaigns often require many rounds to achieve real improvement.
Rational Design
Rational design — by humans or AI — can leap to distant candidates in a single step. But each candidate requires custom synthesis, a significant cost barrier, making high-throughput testing impractical. Most of the space goes untested.
Talaria
Talaria pairs AI-guided design with in-house DNA synthesis. We ship a single pool with up to five million rationally designed, NGS-verified variants. These variants are designed to cover as much of the search space as possible for your protein, resulting in rich functional data. If we don't find a sufficient candidate in our first attempt, our AI models can use this foundational dataset to refine a design for round 2 and to drill deeply into the most performant versions of your protein.