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Characterization of a novel type VII Î²âturn conformation for a bioâactive tetrapeptide rigin: A synergy between theoretical and experimental results
- Ashish,, Grover, Arvinder, Kishore, Raghuvansh
- European journal of biochemistry 2000 v.267 no.5 pp. 1455-1463
- cis-trans isomers, dimethyl sulfoxide, drugs, energy, hydrogen bonding, models, molecular conformation, molecular dynamics, nuclear magnetic resonance spectroscopy, spectral analysis, surveys, temperature
- The conformational analysis of an immunomodulating tetrapeptide rigin (HâGlyâGlnâProâArgâOH), shown to possess diverse immunological activity, has been investigated both theoretically and experimentally for its conformational preferences. Unrestrained molecular dynamics simulation studies in implicit dimethylsulfoxide provide strong support for the existence of a significant population of ordered reverse turn structures for the major trans isomer. Of the three different energy minimized families, generated from computer molecular modelling, only one could be complemented by most of the 1D and 2D 1H NMR parameters obtained in dimethylsulfoxideâd6. A variable temperature NMR experiment in dimethylsulfoxideâd6 revealed that the preferred conformation is not stabilized by an intramolecular hydrogen bonding interaction. An analysis of the 2D ROESY experiment provides evidence in favour of an uncommonly observed, rather illâdefined type VII Î²âturn structure. A survey of the observed specific interâand intraâresidue NOE connectivities and their comparison with one of the predicted lowâenergy conformations, demonstrates synergy between the theoretical molecular modelling and experimentally determined NMR spectral data. The primary structure, rather than longârange interactions, appears to be critical in determining the folding behaviour of the bioâactive rigin. The present structural attributes may be valuable in peptide drug design and development of the rigin analogs having more effective stimulating activity.