title: 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.
abstract: 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.
authors.affiliation: Protein Science & Engineering Division, Institute of Microbial Technology, Sector 39-A, Chandigarh - 160 036, India.
authors.forename: Nigam
authors.initials: N
authors.lastname: Kumar
authors.forename: Raghuvansh
authors.initials: R
authors.lastname: Kishore
mesh_terms: D002942:Circular Dichroism; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012996:Solutions; D014867:Water
chemical_list: D009842:Oligopeptides; D012996:Solutions; D014867:Water; C031491:rigin