%0 Journal Article
%@ 1099-1387
%A Kumar, Nigam
%A Kishore, Raghuvansh
%D 2010
%F open:506
%I Wiley
%J Journal of peptide science : an official publication of the European Peptide Society
%K bioactive peptide; conformational analysis; unusual kinked topology; MD simulations; implicit water; spectroscopic studies
%N 9
%P 456-64
%T Determination of an unusual secondary structural element in the immunostimulating tetrapeptide rigin in aqueous environments: insights via MD simulations, (1)H NMR and CD spectroscopic studies.
%U http://crdd.osdd.net/open/506/
%V 16
%X An immunomodulating tetrapeptide, rigin (H-Gly-Gln-Pro-Arg-OH), has been examined for its secondary structure preferences through combined use of high-temperature unrestrained MD simulations in implicit water and 1D and 2D 1H NMR spectroscopy.The distribution of backbone torsion angles revealed the predominance of trans conformers across the Xaa-Pro peptide bond. The results of MD simulations revealed that of the five predicted families A-E, the predominant families, family A (92 structures), family C (63 structures) and family D (31 structures), could be complemented by extensive 1D and 2D 1H NMR parameters acquired in aqueous PBS solution. A survey of specific inter- and intraresidue NOEs substantiated the predominance of an unusual type VII beta-turn structure, defined by two torsion angles, i.e. psiGln approximately 155 degrees and psiPro approximately -65 degrees across the Gln-Pro segment. The proposed semi-folded kinked topology precluded formation of any intramolecular interaction, i.e. hydrogen bond or electrostatic interaction. Far-UV CD spectral characteristics of rigin in aqueous PBS solution and non-aqueous structure promoting organic solvents, TFE and TMP, revealed its strong solvent dependence. However, in aqueous PBS solution, the presence of a weak negative shoulder at approximately 234 nm could be ascribed to a small population with ordered, semi-folded topology.We propose that the plausible structural attributes may be exploited for design and rigidification of the bioactive conformation of this immunomodulator toward improved immunopharmacological properties.
%Z Copyright of this article belongs to Wiley