NGOME-Lite: Proteome-wide prediction of spontaneous protein deamidation highlights differences between taxa

LORENZO, RAMIRO; LEONETTI, CÉSAR O; ALONSO, LEONARDO G; SÁNCHEZ, IGNACIO E

METHODS

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2020

1046-2023

Asparagines in proteins deamidate spontaneously, which changes the chemicalstructure of a protein and often affects its function. Current prediction algorithms forasparagine deamidation require a structure as an input or are too slow to be applied ata proteomic scale. We present NGOME-Lite, a new version of our sequence-basedpredictor for spontaneous asparagine deamidation that is faster by over two orders ofmagnitude at a similar degree of accuracy. The algorithm takes into account intrinsicsequence propensities and slowing down of deamidation by local structure. NGOMELitecan run in a proteomic analysis mode that provides the half-time of the intact formof each protein, predicted by taking into account sequence propensities and structuralprotection or sequence propensities only, and a structure protection factor. Thedetailed analysis mode also provides graphical output for all Asn residues in the querysequence. We applied NGOME-Lite to over 257000 sequences in 38 proteomes andfound that different taxa differ in their predicted deamidation dynamics. Spontaneousprotein deamidation is faster in Eukarya than in Bacteria because of a higher degree ofstructural protection in the latter. Predicted protein deamidation half-lifes correlate withprotein turnover in human, mouse, rat, C. elegans and budding yeast but not in twoplants and two bacteria. NGOME-Lite is implemented in a docker container available athttp://ngome.proteinphysiologylab.org .