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PLoS Comput Biol. 2016 Apr 20;12(4):e1004786. doi: 10.1371/journal.pcbi.1004786. eCollection 2016 Apr.

Effective Design of Multifunctional Peptides by Combining Compatible Functions.

Author information

1
Department of Biochemistry and Structural Biology, Institute of Cellular Physiology, Universidad Nacional Autónoma de México, Mexico City, Mexico.
2
Department of Biochemistry, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
3
Department of Neurodevelopment and Physiology, Institute of Cellular Physiology, Universidad Nacional Autónoma de México, Mexico City, Mexico.
4
Department of Molecular Medicine and Bioprocesses, Institute of Biotechnology, Universidad Nacional Autónoma de México, Cuernavaca Morelos, México.

Abstract

Multifunctionality is a common trait of many natural proteins and peptides, yet the rules to generate such multifunctionality remain unclear. We propose that the rules defining some protein/peptide functions are compatible. To explore this hypothesis, we trained a computational method to predict cell-penetrating peptides at the sequence level and learned that antimicrobial peptides and DNA-binding proteins are compatible with the rules of our predictor. Based on this finding, we expected that designing peptides for CPP activity may render AMP and DNA-binding activities. To test this prediction, we designed peptides that embedded two independent functional domains (nuclear localization and yeast pheromone activity), linked by optimizing their composition to fit the rules characterizing cell-penetrating peptides. These peptides presented effective cell penetration, DNA-binding, pheromone and antimicrobial activities, thus confirming the effectiveness of our computational approach to design multifunctional peptides with potential therapeutic uses. Our computational implementation is available at http://bis.ifc.unam.mx/en/software/dcf.

PMID:
27096600
PMCID:
PMC4838304
DOI:
10.1371/journal.pcbi.1004786
[Indexed for MEDLINE]
Free PMC Article

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