RESUMO
The ability to rapidly and reliably develop hypotheses on the function of newly discovered protein sequences requires systematic and comprehensive analysis. Such an analysis, embodied within the DS GeneAtlas pipeline, has been used to critically evaluate the severe acute respiratory syndrome (SARS) genome with the goal of identifying new potential targets for viral therapeutic intervention. This paper discusses several new functional hypotheses on the roles played by the constituent gene products of SARS, and will serve as an example of how such assignments can be developed or extended on other systems of interest.
Assuntos
Genoma Viral , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genética , Proteínas Virais/química , Proteínas Virais/genética , Sequência de Aminoácidos , Animais , Sítios de Ligação , DNA Helicases/química , DNA Helicases/genética , RNA Polimerases Dirigidas por DNA/química , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Secundária de Proteína , RNA Helicases/química , RNA Helicases/genética , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/química , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/enzimologia , Alinhamento de Sequência , Análise de Sequência de Proteína , Homologia de Sequência de Aminoácidos , Suínos , Transcrição GênicaRESUMO
To maximise the assignment of function of the proteins encoded by a genome and to aid the search for novel drug targets, there is an emerging need for sensitive methods of predicting protein function on a genome-wide basis. GeneAtlas is an automated, high-throughput pipeline for the prediction of protein structure and function using sequence similarity detection, homology modelling and fold recognition methods. GeneAtlas is described in detail here. To test GeneAtlas, a 'virtual' genome was used, a subset of PDB structures from the SCOP database, in which the functional relationships are known. GeneAtlas detects additional relationships by building 3D models in comparison with the sequence searching method PSI-BLAST. Functionally related proteins with sequence identity below the twilight zone can be recognised correctly.