Toward direct determination of conformations of protein building units from multidimensional NMR experiments I. A theoretical case study of For-Gly-NH2 and For-L-Ala-NH2

NMR chemical shielding anisotropy tensors have been computed, employing sev eral basis sets and the GLAO-RHF and GIAO-MP2 formalisms of electronic stru cture theory, for all the atoms of the five and nine typical backbone confo rmers of For-Gly-NH2 and For r-Ala-NH2, respectively. Multidimensional chem ical shift plots, as a function of the respective backbone fold, have been generated for both peptide models. On the 2D (HNNH)-H-1-N-NH_15 and (NCalph a)-N-15-C-NH_13 Plots the most notable feature is that at all levels of the ory studied the backbone conformers cluster in different regions. Computed chemical shifts, as well as their averages, have been compared to relevant experimental values taken from the BioMagnetic Resonance Bank (BMRB). At th e highest levels of theory, for all nuclei but the amide protons, deviation s between statistically averaged theoretical and experimental shifts are as low as 1-3%. These results indicate that chemical shift information from s elected multiple-pulse NMR experiments (e.g., 2D-HSQC and 3D-HNCA) could di rectly be employed to extract folding information for polypeptides and prot eins. (C) 2000 John Wiley & Sons, Inc.