Prediction of enzyme function based on 3D templates of evolutionarily important amino acids

BMC Bioinformatics
David M KristensenOlivier Lichtarge

Abstract

Structural genomics projects such as the Protein Structure Initiative (PSI) yield many new structures, but often these have no known molecular functions. One approach to recover this information is to use 3D templates - structure-function motifs that consist of a few functionally critical amino acids and may suggest functional similarity when geometrically matched to other structures. Since experimentally determined functional sites are not common enough to define 3D templates on a large scale, this work tests a computational strategy to select relevant residues for 3D templates. Based on evolutionary information and heuristics, an Evolutionary Trace Annotation (ETA) pipeline built templates for 98 enzymes, half taken from the PSI, and sought matches in a non-redundant structure database. On average each template matched 2.7 distinct proteins, of which 2.0 share the first three Enzyme Commission digits as the template's enzyme of origin. In many cases (61%) a single most likely function could be predicted as the annotation with the most matches, and in these cases such a plurality vote identified the correct function with 87% accuracy. ETA was also found to be complementary to sequence homology-based annotations. When matches a...Continue Reading

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Software Mentioned

GASPS
Spider package
MA
PDBSiteScan
Cavbase
MATLAB
Evolutionary Trace ( ET ) Trace Annotation ETA
PDBFun
VAST
ConSurf

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