flora a novel method to predict protein function from structure in diverse superfamilies植物一种新颖的方法来预测蛋白质功能结构的多样化的总科.pdfVIP

FLORA: A Novel Method to Predict Protein Function from Structure in Diverse Superfamilies ˆ Oliver C Redfern*, Benoıt H Dessailly, Timothy J Dallman, Ian Sillitoe, Christine A Orengo Research Department of Structural and Molecular Biology, University College London, London, United Kingdom Abstract Predicting protein function from structure remains an active area of interest, particularly for the structural genomics initiatives where a substantial number of structures are initially solved with little or no functional characterisation. Although global structure comparison methods can be used to transfer functional annotations, the relationship between fold and function is complex, particularly in functionally diverse superfamilies that have evolved through different secondary structure embellishments to a common structural core. The majority of prediction algorithms employ local templates built on known or predicted functional residues. Here, we present a novel method (FLORA) that automatically generates structural motifs associated with different functional sub-families (FSGs) within functionally diverse domain superfamilies. Templates are created purely on the basis of their specificity for a given FSG, and the method makes no prior prediction of functional sites, nor assumes specific physico-chemical properties of residues. FLORA is able to accurately discriminate between homologous domains with different functions and substantially outperforms (a 2–3 fold increase in coverage at low error rates) popular structure comparison methods and a leading function prediction method. We benchmark FLORA on a large data set of enzyme superfamilies from all three major protein classes (a, b, ab) and demonstrate the functional relevance