Integrating protein structures and precomputed genealogies in the Magnum database: examples with cellular retinoid binding proteins

BMC Bioinformatics
Michael E Bradley, S A Benner

Abstract

When accurate models for the divergent evolution of protein sequences are integrated with complementary biological information, such as folded protein structures, analyses of the combined data often lead to new hypotheses about molecular physiology. This represents an excellent example of how bioinformatics can be used to guide experimental research. However, progress in this direction has been slowed by the lack of a publicly available resource suitable for general use. The precomputed Magnum database offers a solution to this problem for ca. 1,800 full-length protein families with at least one crystal structure. The Magnum deliverables include 1) multiple sequence alignments, 2) mapping of alignment sites to crystal structure sites, 3) phylogenetic trees, 4) inferred ancestral sequences at internal tree nodes, and 5) amino acid replacements along tree branches. Comprehensive evaluations revealed that the automated procedures used to construct Magnum produced accurate models of how proteins divergently evolve, or genealogies, and correctly integrated these with the structural data. To demonstrate Magnum's capabilities, we asked for amino acid replacements requiring three nucleotide substitutions, located at internal protein st...Continue Reading

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Citations

Dec 11, 2008·Journal of Molecular Evolution·Michael E BradleyNancy B Schwartz

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Datasets Mentioned

BETA
XP422636
DN068529

Methods Mentioned

BETA
phylogenetic sequence

Software Mentioned

ClustalW
Ancescon
DARWIN package
MasterCatalog
MySQL
MathType
PERL
Magnum
Seq2Struct
Pisces

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