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Folding propensity and biological activity of peptides: The effect of a single stereochemical isomerization on the conformational properties of bombinins in aqueous solution
Author(s) -
Bozzi Argante,
Mangoni Maria Luisa,
Rinaldi Andrea C.,
Mignogna Giuseppina,
Aschi Massimiliano
Publication year - 2008
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21006
Subject(s) - chemistry , molecular dynamics , folding (dsp implementation) , isomerization , circular dichroism , peptide , stereochemistry , protein folding , aqueous solution , crystallography , computational chemistry , organic chemistry , biochemistry , catalysis , electrical engineering , engineering
Folding propensities of bombinins H2 and H4, two members of amphibian bombinins H, a family of 17–20 residue α‐helical peptides, have been investigated by means of circular dichroism (CD) measurements and molecular dynamics (MD) simulations. The two peptides, with primary structure IIGPVLGLVGSALGGLLKKI‐NH2 and differing only for the configuration of the second aminoacid (an L‐isoleucine in H2 and a D‐alloisoleucine in H4) behave rather differently in solution. In particular both CD measurements and MD simulations indicate that bombinin H2 shows a markedly higher tendency to fold. From a careful inspection of MD trajectories it emerges that the stereochemical isomerization mutation of residue 2 to D‐alloisoleucine in H4 peptide, drastically decreases its ability to form intrapeptide contacts. MD simulations also indicate that the conformational sampling in both systems derives from a subtle combination of energetic and entropic effects both involving the peptide itself and the solvent. The present results have been finally paralleled with preliminary information on bombinins H2 and H4 biological activity, i.e. interaction with membrane, supporting the hypothesis of an “already folded” conformation in water rather than interfacial folding tenet. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 769–778, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com