Conservation Weighting Functions Enable Covariance Analyses to Detect Functionally Important Amino Acids

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Conservation Weighting Functions Enable Covariance Analyses to Detect Functionally Important Amino Acids

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Title: Conservation Weighting Functions Enable Covariance Analyses to Detect Functionally Important Amino Acids
Author: Colwell, Lucy J.; Brenner, Michael P.; Murray, Andrew W.

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Citation: Colwell, Lucy J., Michael P. Brenner, and Andrew W. Murray. 2014. “Conservation Weighting Functions Enable Covariance Analyses to Detect Functionally Important Amino Acids.” PLoS ONE 9 (11): e107723. doi:10.1371/journal.pone.0107723. http://dx.doi.org/10.1371/journal.pone.0107723.
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Abstract: The explosive growth in the number of protein sequences gives rise to the possibility of using the natural variation in sequences of homologous proteins to find residues that control different protein phenotypes. Because in many cases different phenotypes are each controlled by a group of residues, the mutations that separate one version of a phenotype from another will be correlated. Here we incorporate biological knowledge about protein phenotypes and their variability in the sequence alignment of interest into algorithms that detect correlated mutations, improving their ability to detect the residues that control those phenotypes. We demonstrate the power of this approach using simulations and recent experimental data. Applying these principles to the protein families encoded by Dscam and Protocadherin allows us to make testable predictions about the residues that dictate the specificity of molecular interactions.
Published Version: doi:10.1371/journal.pone.0107723
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224327/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:13454695
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