Molecular modeling of four Dermaseptin-related peptides of the gliding tree frog Agalychnis spurrelli
In this research, we present a preliminary computational study of four Dermaseptin-related peptides from the skin exudate of the gliding tree frog Agalychnis spurrelli. Experimentally, the amino acid sequence of these peptides was elucidated through molecular cloning and tandem mass spectrometry and synthetic peptides were assayed against E. coli, S. aureus, and C. albicans to determine their antimicrobial properties. With the sequences on hand, a computational study of the structures was carried out, obtaining their physicochemical properties, secondary structure, and their similarity to other known peptides. A molecular docking study of these peptides was also performed against cell membrane and several enzymes are known to be vital for the organisms. Results showed that Dermaseptin-related peptides are α-helical cationic peptides with an isoelectric point above 9.70 and a positive charge of physiological pH. Introducing theses peptides in a database, it was determined that their identity compared with known peptides range from 36 to 82% meaning these four Dermaseptins are novel peptides. This preliminary study of molecular docking suggests the mechanism of action of this peptide is not given by the inhibition of essential enzymatic pathways, but by cell lysis.
KeywordsAgalychnis spurrelli Antimicrobial peptides Dermaseptins Molecular docking
CPB obtained the peptides sequences in Queen’s University Belfast funded by the Natural drug discovery group and the Ecuadorian Secretariat of Science and Technology (SENESCYT) through a scholarship. Collection and rearing of frogs in Ecuador were done under permits of the Ecuadorian Ministerio de Ambiente (MAE): 001-13 IC-FAU-DNB/MA, 003-11 IC-FAU-DNB/MA, 005-15 IC-FAU-DNB/MA (Issued to the Centro Jambatu). This research is part of the project “Conservation of Ecuadorian amphibian diversity and sustainable use of its genetic resources”, which involves MAE, Ikiam-Universidad Regional Amazónica, Queen’s University Belfast, and Centro Jambatu, and help of the Global Environmental Facility (GEF) and “Programa de las Naciones Unidas para el Desarrollo” (PNUD).
This research was funded by two research grants to L.M and M.R. of the Dirección General Académica of the Pontificia Universidad Católica del Ecuador, projects: QINV0035-IINV529010100 and QIV0046-IINV529010100.
- 1.Conlon JM (2012) The potential of frog skin antimicrobial peptides for development into therapeutically valuable anti-infective agents, Chapter 3 In Small Wonders. Peptides for Disease Control; ACS Symposium Series; American Chemical Society, WashingtonGoogle Scholar
- 2.Lacombe C, Piesse C, Sagan S, Combadière C, Rosenstein Y, Auvynet C (2015) Pachymodulin, a new functional formyl peptide receptor 2 peptidic ligand isolated from frog skin has Janus-like immunomodulatory capacities. J Med Chem 58:1089–1099. https://doi.org/10.1021/jm501018q CrossRefPubMedGoogle Scholar
- 3.Holthausen D, Lee S, Kumar V, Bouvier N, Krammer F, Ellebedy A, Wrammert J, Lowen A, George S, Pillai M, Jacob J (2017) An amphibian host defense peptide is virucidal for human H1 hemagglutinin-bearing influenza viruses. Immunity 46:587–595. https://doi.org/10.1016/j.immuni.2017.03.018 CrossRefPubMedGoogle Scholar
- 4.Scorciapino M, Manzo G, Rinaldi A, Sanna R, Casu M, Pantic J, Lukic M, Conlon J (2013) Conformational analysis of the frog skin peptide, plasticin-L1 and its effects on the production of proinflammatory cytokines by macrophages. Biochemistry 52(41):7231–7241. https://doi.org/10.1021/bi4008287 CrossRefPubMedGoogle Scholar
- 5.Manzo G, Casu M, Rinaldi M, Montaldo N, Luganini A, Gribaudo G, Scorciapino M (2014) Folded structure and insertion depth of the frog-skin antimicrobial peptide esculentin-1b (1–18) in the presence of differently charged membrane-mimicking micelles. J Nat Prod 77(11):2410–2417. https://doi.org/10.1021/np5004406 CrossRefPubMedGoogle Scholar
- 7.Marani M, Dourado F, Quelemes P, Rodrigues A, Gomes M, Alves E, Costa L, Rodrigues A, Barroso E, Eaton P, Figueiró J, Bentes R, Delerue-Matos C, Leite J (2015) Characterization and biological activities of ocellatin peptides from the skin secretion of the frog Leptodactylus pustulatus. J Nat Prod 78(7):1495–1504. https://doi.org/10.1021/np500907t CrossRefPubMedGoogle Scholar
- 8.Stutz K, Muller A, Hiss J, Schneider P, Blatter M, Pfeiffer B, Posselt G, Kanfer G, Kornmann B, Wrede P, Altmann K, Wessler S, Schneider G (2017) Peptide-membrane interaction between targeting and lysis. ACS Chem Biol 12(9):2254–2259. https://doi.org/10.1021/acschembio.7b00504 CrossRefPubMedGoogle Scholar
- 10.Duellman WE (2001) Hylid Frogs of Middle America. Society for the Study of Amphibians and Reptiles, IthacaGoogle Scholar
- 11.Gray AR (1997) Observations on the biology of Agalychnis spurrelli from the Caribbean lowlands of Costa Rica. Observaciones sobre la biología de Agalychnis spurrelli de las tierras bajas del caribe de Costa Rica. Journal of the International Herpetological Society 22:61–70Google Scholar
- 12.MECN (2010) Serie Herpetofauna del Ecuador: El Choco Esmeraldeño. Monografía. Museo Ecuatoriano de Ciencias Naturales. Quito-Ecuador 5:1–232Google Scholar
- 13.Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins MR, Appel RD, Bairoch A (2005) Protein Identification and Analysis Tools on the ExPASy Server. In: En Walker J (ed) The Proteomics Protocols Handbook. Springer, LondonGoogle Scholar
- 14.Innovagen (2015) Peptide property calculator, Innovagen AB, https://pepcalc.com/
- 15.Bio-Synthesis. (2018). Peptide Property Calculator, Bio-Synthesis Inc. https://www.biosyn.com/peptidepropertycalculatorlanding.aspx
- 18.The PyMOL Molecular Graphics System (2017) Version 2.0 Schrödinger, LLC. https://pymol.org/2/support.html?#citing
- 19.ChembioDraw (2009) PerkinElmer Informatics. http://informatics.perkinelmer.com/Support/KnowledgeBase/details/Default?TechNote=3411
- 30.Melchiorri P, Negri L (2009) Amphibian peptides, Encyclopedia of Neuroscience. Elsevier Academic Press, San DiegoGoogle Scholar
- 33.Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M (2017) DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res 46:1074–1082CrossRefGoogle Scholar