Ab Initio prediction of mycobacteriophages protein structure and function
BMC Bioinformatics volume 14, Article number: A10 (2013)
Mycobacterium smegmatis is a soil bacterium. Over 448 mycobacteriophages specific for M. smegmatis have been sequenced and grouped into clusters of related genomes based on the similarity of their products and genome organization. Only 20% of mycobacteriophage genes have known function, as predicted by protein sequence level alignments .
Materials and methods
Genes that are grouped together using BLAST at the protein sequence level have been assembled into loose groupings called phams . The phagesdb.org/phams database contains the protein sequences organized by phams. From these data we used ab initio folding, using I-TASSER , to predict the structure of multiple phams across numerous mycobacteriophage clusters. Predicted models were grouped into structural families based upon RMSD scores from pairwise comparisons. Models from two structural families per pham were submitted to COFACTOR , which finds the best structural homologies to proteins in the PDB library and returns the matching structures along with GO terms, EC numbers and active site information.
Based on COFACTOR output, we were able to suggest functions for the genes in each respective pham examined. Two notable results: 1) pham 6714 is predicted to be a methyltransferase (Figure 1), and 2) pham 2789 is predicted to be either a neutral endopeptidase (Figure 2a) or an importin protein (Figure 2b). These predicted functions will need to be confirmed experimentally.
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Kapadia, C.D., Rinehart, C.A. Ab Initio prediction of mycobacteriophages protein structure and function. BMC Bioinformatics 14 (Suppl 17), A10 (2013). https://doi.org/10.1186/1471-2105-14-S17-A10