By smaller peptide I mean somewhere around 15-20 aminoacids, having a cycle or two that constrain the geometry.
Also - I am interested in getting as much detail about the structure of the peptide as possible.
Do you typically need to record NOE buildup curves in such cases?
Given that side-chains of the peptide are unlikely to be packed like in the core of the globular protein - do you include side-chain NOE's into structure calculations?
Could you recommend any citations?
There is a fundamental difference between the use of solution NMR spectroscopy for conformational analysis of peptides and globular proteins.
In the case of globular proteins, the fundamental assumption is that a single conformation can explain most of the observable data regarding NOe's, coupling constants, etc. An ensemble is generated, but each member of the ensemble is (usually) assumed to be an equally good model for the observable data.
In most smaller peptides, we can no longer assume that a single dominant conformation exists, even for the backbone. I did some work with cyclic tetrapeptides, and found evidence for conformational flexibility of the backbone. We would expect greater conformational heterogeneity in the larger peptides that you have mentioned. Therefore, the presence of a cycle does guarantee rigidness of the backbone in small to medium sized peptides. Therefore, the fact that all observables (e.g. Noe's, coupling constants, chemical shifts) are ensemble averages has to be explicitly included in the conformational analysis. This usually involves generating a large number of low energy structures and determination of the relative weight of each conformer by empirical fit to the entire observable data. Often, the experimental data is inadequate for such detailed analysis.
Structural conclusions regarding peptides may also obtained, based on qualitative analysis. For example, i->i+2 and i->i+3 Noe's and other long range NOe's are 'not observable*' in most peptides; therefore, if you observe non-sequential NOe's in you peptide then you can conclude that a 'significant' fraction of the conformational ensemble consists of conformations with defined secondary structure (e.g. beta-turns). These conclusions can be validated by obtaining NMR data on peptide analogs, and showing that the non-sequential NOe's observed in the peptide of interest are not present in peptides analogs of similar size, topology and composition under the same set of experimental conditions.
*Note:this would of course depend on experimental conditions such as peptide concentration, probe sensitivity, NOe mixing time etc.
Polyproline II conformation is one of many local conformational states and is not an overall conformation of unfolded peptides and proteins. Joanna Makowska,Sylwia Rodziewicz-Motowidlo, Katarzyna Baginska, Jorge A. Vila, Adam Liwo, Lech Chmurzynski, and Harold A. Scheraga PNAS February 7, 2006 vol. 103 no. 6 1744-1749.
Exploration of the conformational space of oxytocin and arginine-vasopressin using the electrostatically driven Monte Carlo and molecular dynamics methods. Biopolymers. Volume 38 Issue 2, Pages 157 - 175.
C. M. Falcomer, Y. C. Meinwald, I. Choudhary, S. Talluri, P.W.Millburn, J.C.Clardy and H. A. Scheraga "Chain reversals in model peptides: Studies of cystine-containing cyclic peptides. Conformational energies of cyclization of tetrapeptides of sequence Ac-Cys-Pro-X-Cys-NHMe." Journal of the American Chemical Society, 114, 4036 (1992).