#27 · Structural bio & protein design

Simulated evolution tests recovery of ancestral and intermediate sequences

The dominant thread is benchmarking sequence reconstruction against known evolutionary truth. Two preprints dated 2026-06-26 evaluate inference of ancestral and intermediate sequences using simulated evolution. One combines phylogenetic inference with Direct Coupling Analysis for coevolution-aware ancestral sequence reconstruction, benchmarked via forward evolution. The other tests data-driven reconstruction of evolutionary intermediates on generative epistatic landscapes against simulated ground-truth trajectories. What is new is the use of simulated evolutionary truth to test whether methods recover intermediates and coupling-aware ancestors. A third preprint, a large-scale computational characterization of a protein secondary structure genotype-to-phenotype map using an AVR3a effector domain, is adjacent in topic but does not perform reconstruction benchmarking.