Know Your Alphabet: Conformational Noise, Latent-Space Encodings, and the Future of Structural Phylogenetics (opens in new tab)

Structural alphabets have transformed protein phylogenetics by enabling sequence-style alignment and maximum-likelihood inference to be applied directly to structural data. However, a coordinate-explicit alphabet, in which character states are derived from three-dimensional atomic positions, encodes not only evolutionary signal but also the conformational variability inherent to protein structure. This source of noise has not previously been quantified in a phylogenetic context, and no framew...