Considerations for Predicting Peptides of the Insect Adipokinetic Hormone Ensemble Using Sequence Alignment

Background: Adipokinetic hormones (AKHs) are metabolic regulators in insects, and many are still unknown. Bioinformatic analysis can assist entomologic research with predictions based on sequence similarity. Methods: AKHs are short peptides with specific sequence features, which were used together with the rules for preprohormone processing to interrogate National Center for Biotechnology Information (NCBI) genomic/transcriptomic data for novel putative AKH sequences by sequence alignment and similarity search. The structures of the signal peptide processing site and the dibasic processing site were evaluated in known and predicted AKHs. Results: 28 novel AKHs were predicted, as well as 8 peptides likely belonging to the AKH/corazonin-related peptide family. Furthermore, the presence of 42 known AKHs was suggested in 162 species, which have not yet been investigated experimentally for such peptide hormones. The dibasic processing site in known AKHs was almost exclusively sequence tag GKR. For the signal peptide processing site, residues A/C/G/S/T/V were mostly found in the –3-position and A/C/G/S in the –1-position. The results were assembled in a searchable archive of validated (from the literature), predicted (obtained by sequence search), and hypothetical (from combinatorial calculation) amino acid sequences, including taxonomy criteria and mass information. Conclusions: The archive is a snapshot of the current AKH landscape and useful as a reference and research tool. It allows grouping and sorting the entries for, e.g., order-specific sequences or peptide ion m/z values, and thus assists, among other purposes, chemical analysis with hypotheses for the identification of hormones in newly investigated species. The systematic comparison of the observed structures of the processing sites helps in future sequence evaluations for predicted AKHs.