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Structural analysis of substance P using molecular dynamics and NMR spectroscopy
Author(s) -
Corcho Francesc J.,
Salvatella Xavier,
Canto Josep,
Giralt Ernest,
Perez Juan J.
Publication year - 2007
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.880
Subject(s) - molecular dynamics , chemistry , nuclear magnetic resonance spectroscopy , peptide , peptide sequence , structural motif , n terminus , sequence (biology) , stereochemistry , two dimensional nuclear magnetic resonance spectroscopy , resonance (particle physics) , molecular model , protein structure , computational chemistry , biochemistry , gene , physics , particle physics
The present work is a combined structural study, using Nuclear Magnetic Resonance (NMR) and Molecular Dynamics(MD), of the amidated and the free acid forms of substance P in water and methanol. The results obtained using both approaches were compared in order to characterize the structural features of both peptides in solution. From the NMR experiments it was derived that the free acid form adopts an extended conformation at the N ‐terminus and a helical conformation at the C ‐terminal segment of the peptide in both water and methanol; these structural features are in qualitative agreement with the results of the MD simulations. No significant differences in behavior were observed between the amidated and the free acid forms of the peptide in the simulations and in the experiments carried out in water, suggesting that the different activities of these analogs are due to their different mode of interaction with the receptor rather than to their structural preferences. Finally, we propose that the structure of substance P can be partially inferred from its sequence due to the presence of a Pro‐X‐Pro motif on the N ‐terminus and a Gly–Leu sequence on the C ‐terminus. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.