Unlocking Protein Potential: EvoSelect® and Directed Evolution

In biotechnology, protein engineering is essential for developing new solutions across various fields. At Isomerase, we are leading this effort with tools like EvoSelect®, our protein computational tool, to drive innovation and speed up progress through directed evolution.

Directed Evolution of Enzymes via EvoSelect®.

Enhancing Protein Functionality

EvoSelect® is our computational workhorse—a tool that simulates protein evolution with remarkable precision. How does it work? By modeling protein sequences using the Potts model using data from public and proprietary genome sequences, EvoSelect® predicts evolutionary fitness and iteratively mutates sequences to achieve desired properties. The outcome? A library of protein variants, each more likely to demonstrate improved function than random mutagenesis strategies.

Pairwise Dependencies and Beyond

Unlike traditional methods, EvoSelect® incorporates pairwise relationships across protein sequences. Why is this crucial? Because it allows us to capture epistatic effects—interdependencies between residues. These interactions influence protein stability, function, and structure. By harnessing this knowledge, we can design variants with as little as 50% sequence similarity to the original protein while retaining critical functionality—a phenomenon akin to convergent evolution.

Applications and Future Prospects

Tailored Therapeutics

EvoSelect® isn’t just theoretical—it’s practical. We have used it to generate enzymes with improved protein activity and thermostability. By using custom curated databases with proprietary genome sequences we can direct the evolution of proteins towards distinct traits such as thermostability.

Reducing Experimental Burden

Experimental burden in directed evolution pipelines is significantly reduced when coupled with EvoSelect®. Instead of exploring vast sequence spaces (10¹³⁰ possible variants for a 100 amino acid protein sequence) we restrict this space using evolutionary information. The result is that EvoSelect® generated variants by minimum are functional and by standard have improved properties, reducing the number of variants to screen from upwards of 1x10¹¹ [1] to 10s or 100s of sequences. This reduces the cost of directed evolution making it practical on a much wider range of projects.

Industrial Applications

EvoSelect®’s applications are general and diverse, applying particularly well to industry, from biocatalytic enzymes to sustainable materials, we’re exploring diverse domains. EvoSelect® enables us to engineer proteins for biocatalysis, biosynthesis, and environmental remediation.

Conclusion

At Isomerase, we’re not just decoding protein sequences; we’re rewriting their potential. EvoSelect® is our compass, guiding us toward innovative solutions. Join us on this exciting journey as we unlock the secrets of protein evolution—one variant at a time. If you are interested in incorporating EvoSelect® into your project, please contact our team.