PASTA 2.0: an improved server for protein aggregation prediction.
The formation of amyloid aggregates upon protein misfolding is related to several devastating degenerative diseases. The propensities of different protein sequences to aggregate into amyloids, how they are enhanced by pathogenic mutations, the presence of aggregation hot spots stabilizing pathological interactions, the establishing of cross-amyloid interactions between co-aggregating proteins, all rely at the molecular level on the stability of the amyloid cross-beta structure. Our redesigned server, PASTA 2.0, provides a versatile platform where all of these different features can be easily predicted on a genomic scale given input sequences. The server provides other pieces of information, such as intrinsic disorder and secondary structure predictions, that complement the aggregation data. The PASTA 2.0 energy function evaluates the stability of putative cross-beta pairings between different sequence stretches. It was re-derived on a larger dataset of globular protein domains. The resulting algorithm was benchmarked on comprehensive peptide and protein test sets, leading to improved, state-of-the-art results with more amyloid forming regions correctly detected at high specificity. The PASTA 2.0 server can be accessed at http://protein.bio.unipd.it/pasta2/.
Department of Biomedical Sciences, University of Padova, Padova I-35131, Italy.
Ian
I
Walsh
INFN, Padova Section, and Department of Physics and Astronomy 'G. Galilei', University of Padova, Padova I-35121, Italy.
Flavio
F
Seno
Department of Biomedical Sciences, University of Padova, Padova I-35131, Italy silvio.tosatto@unipd.it.
Silvio C E
SC
Tosatto
INFN, Padova Section, and Department of Physics and Astronomy 'G. Galilei', University of Padova, Padova I-35121, Italy.
Antonio
A
Trovato
D000465:Algorithms; D000682:Amyloid / Q000737:chemistry* / Q000235:genetics; D020407:Internet; D064267:Intrinsically Disordered Proteins / Q000737:chemistry; D010455:Peptides / Q000145:classification; D017354:Point Mutation; D017433:Protein Structure, Secondary; D020539:Sequence Analysis, Protein; D012984:Software
D000682:Amyloid; D064267:Intrinsically Disordered Proteins; D010455:Peptides