Evolutionary distances for protein-coding sequences: modeling site-specific residue frequencies.

@article{Halpern1998EvolutionaryDF,
  title={Evolutionary distances for protein-coding sequences: modeling site-specific residue frequencies.},
  author={Anne L. Halpern and William J. Bruno},
  journal={Molecular biology and evolution},
  year={1998},
  volume={15 7},
  pages={
          910-7
        }
}
Estimation of evolutionary distances from coding sequences must take into account protein-level selection to avoid relative underestimation of longer evolutionary distances. Current modeling of selection via site-to-site rate heterogeneity generally neglects another aspect of selection, namely position-specific amino acid frequencies. These frequencies determine the maximum dissimilarity expected for highly diverged but functionally and structurally conserved sequences, and hence are crucial… 
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