Harvard Study: Designing Protein Variants of Altered Specificity via Model Differences
AllThingsApx · x · 2026-08-02
A research team from Harvard Medical School published a new paper on bioRxiv regarding protein engineering. The study points out that directed evolution struggles to efficiently traverse the fitness landscape within the vastness of sequence space.
While unsupervised probabilistic models (PLMs) trained on natural sequences have shown promise for predicting mutation effects, PLMs tend to suggest variants that conserve similar binding characteristics as the template sequence. The researchers propose that differences between protein fitness models can be utilized to design protein variants with altered specificity, such as evolving new substrates or ligands.
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