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Divergent evolution has created multiple catalytic capabilities within active sites of common structural organization. Understanding the structure-functional relationship of homologous diverged active sites capable to perform different chemical transformations is one of major challenges for modern enzymology that can be tackled using Zebra.

In order to evaluate the ability of Zebra to predict experimentally confirmed specific positions bioinformatic analysis was performed of glutathione S-transferase superfamily, guanylyl/adenylyl cyclases and β/α-barrel fold basic amino acid decarboxylases. In addition to those specific examples, quantitative assessment and comparison with previously published algorithms was done on large datasets.