Sequence-structure-function paradigm

The following sections briefly discuss some results and trends in using structure prediction for remote homology detection especially in the genomic context, to aid the structural genomics projects, to further whole genome annotation and to exploit the sequence-to-structure-to-function paradigm for functional predictions. 

In general, this sequence-to-structure-to-function paradigm involves predicting a structural model for a given sequence (either by sequence and/or structural means, e.g. threading) and, afterwards, identifying a 3D pattern,... 

Fetrow, J. S. and J. Skolnick, Method for prediction of protein function from sequence using the sequence-to-structure-to-function paradigm with application to glutaredoxins/thioredoxins and T1 ribonucleases. J Mol Biol, 1998. 281(5) p. 949-68. 

In order to relate structure and function at a more direct level, it is necessary to focus on systems which have better characterized structure than the complex membrane bound proteins like cyt c oxidase. One particularly useful paradigm in this context is the cytochrome c-cytochrome c peroxidase couple [18]. Cep is not involved in electron transport, per se its apparent function [19] is detoxification of hydrogen peroxide via the sequence H2O2 -I- cep Fe(III) -> H2O -I- cep Fe(IV) O (protein) compound ES ... 

The major paradigm of structural biology is that the amino acid sequence determines protein structure and function. Recent advances in understanding protein dynamics calls for an extension of this picture by including that protein dynamics, essentially coupled to function, is also encoded in the primary... 

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