Eur. Phys. J. D 20, 513-530 (2002)
https://doi.org/10.1140/epjd/e2002-00157-4

Toward direct determination of conformations of protein building units from multidimensional NMR experiments III

A theoretical case study of For–L-Phe–NH

¹ Department of Organic Chemistry, Eötvös University, P.O. Box 32, 1518 Budapest 112, Hungary
² Department of Theoretical Chemistry, Eötvös University, P.O. Box 32, 1518 Budapest 112, Hungary

Corresponding authors: ^a perczel@para.chem.elte.hu - ^b csaszar@chem.elte.hu

Received: 10 January 2002
Published online: 13 September 2002

Abstract

Chemical shielding anisotropy tensors have been determined, within the GIAO-RHF formalism using a smaller [6-31+G(d)] and two medium-size basis sets [6-311++G(d,p) and TZ2P], for all elements of the conformational library (altogether 27 structures) of the hydrophobic model peptide For–L-Phe–NH₂. The individual chemical shifts and their conformational averages have been compared to their experimental counterparts taken from the BioMagnetic Resonance Bank (BMRB). At the highest level of theory applied, for all nuclei but the amide proton, deviations between statistically averaged theoretical and experimental chemical shifts are as low as a few percent. One-dimensional (1D) chemical shift – structure plots do not allow unambiguous identification of backbone conformations. On the other hand, on chemical shift – chemical shift plots of selected nuclei, e.g., ¹H^N with ¹⁵N or ¹⁵N with ¹³C, regions corresponding to major conformational motifs have been found, providing basis for the identification of peptide conformers solely from NMR shift data. The 2D ¹H–¹³C as well as the 3D ¹H–¹³C–¹³C chemical shift – chemical shift plots appear to be of special importance for direct determination of conformations of protein building units from multidimensional NMR experiments. 48 pairs of ¹H–¹³C data for phenylalanine residues have been extracted from 18 selected proteins and compared to relevant ab initio results, supporting the calculated results. Thus, the appealing idea of establishing backbone folding information of peptides and proteins from chemical shift information alone, obtained from selected multiple-pulse NMR experiments (e.g., 2D-HSQC, 2D-HMQC, and 3D-HNCA), has received further support.