Conservation weighting functions enable covariance analyses to detect functionally important amino acids

Abstract

The explosive growth in the number of protein sequences gives rise to the possibility of using the natural variation in homologous proteins to find residues that control different protein phenotypes. Because in many cases are each controlled by a group of residues, the mutations that separate one version of a phenotype will be correlated. Here we incorporate biological knowledge about protein phenotypes and their variability in alignment of interest into algorithms that detect correlated mutations, improving their ability to detect the control those phenotypes. We demonstrate the power of this approach using simulations and recent. Applying these principles to the protein families encoded by Dscam and Protocadherin allows us to make about the residues that dictate the specificity of molecular interactions.