Plos iconPlosSep 3, 2026 ~1 min source read

Sequence-free landscape inference for directed evolution

The process of protein directed evolution can be envisaged as navigation over high-dimensional optimisation landscapes with numerous local maxima. The performance of any strategy in navigating such a landscape is dependent on the ruggedness of that landscape.

Sequence-free landscape inference for directed evolution

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The process of protein directed evolution can be envisaged as navigation over high-dimensional optimisation landscapes with numerous local maxima.

The performance of any strategy in navigating such a landscape is dependent on the ruggedness of that landscape.

However, this information is generally unavailable at the outset of an experiment.

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The useful part

The process of protein directed evolution can be envisaged as navigation over high-dimensional optimisation landscapes with numerous local maxima. The performance of any strategy in navigating such a landscape is dependent on the ruggedness of that landscape. However, this information is generally unavailable at the outset of an experiment.

How it works

  • Such ruggedness information in itself is valuable in protein design, for instance in predicting evolutionary stability.
  • Second, SLIDE offers a framework for using the estimated ruggedness metric to identify high-performing selection strategies for directed evolution.
  • Here we propose SLIDE, Sequence-free Landscape Inference for Directed Evolution, which consists of two parts.

Details worth keeping

by Sebastian Towers, Jessica James, Harrison Steel, Idris Kempf Directed evolution is a method for engineering biological systems or components, such as proteins, wherein desired traits are optimised through iterative rounds of mutagenesis and selection of fit variants. Using theoretical NK landscapes and four empirical protein fitness landscapes, we demonstrate consistent in silico improvement upon the performance of fixed-parameter strategies, using a pipeline that could also be combined with emerging AI-based methods for driving directed evolution.

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