Untitled

Abstract

The importance of protein chemical shift values for the determination of three-dimensional protein structure has increased in recent years because of the large databases of protein structures with assigned chemical shift data. These databases have allowed the investigation of the quantitative relationship between chemical shift values obtained by liquid state NMR spectroscopy and the three-dimensional structure of proteins. A neural network was trained to predict the (1)H, (13)C, and (15)N of proteins using their three-dimensional structure as well as experimental conditions as input parameters. It achieves root mean square deviations of 0.3 ppm for hydrogen, 1.3 ppm for carbon, and 2.6 ppm for nitrogen chemical shifts. The model reflects important influences of the covalent structure as well as of the conformation not only for backbone atoms (as, e.g., the chemical shift index) but also for side-chain nuclei. For protein models with a RMSD smaller than 5 A a correlation of the RMSD and the r.m.s. deviation between the predicted and the experimental chemical shift is obtained. Thus the method has the potential to not only support the assignment process of proteins but also help with the validation and the refinement of three-dimensional structural proposals. It is freely available for academic users at the PROSHIFT server: www.jens-meiler.de/proshift.html

Differential dynamics in the G protein-coupled receptor rhodopsin revealed by solution NMR

“…15 N chemical shifts were calculated by using the programs SHIFTS (13) and PROSHIFT (14). 1 H chemical shifts were calculated by using the programs PROSHIFT (14) and SHIFTCALC (15).…”

“…15 N chemical shifts were calculated by using the programs SHIFTS (13) and PROSHIFT (14). 1 H chemical shifts were calculated by using the programs PROSHIFT (14) and SHIFTCALC (15). All programs were applied to both chains in the two available crystal structures with Protein Data Bank (PDB) ID codes 1F88 (resolution 2.8 Å) and 1L9H (resolution 2.6 Å), and the eight values were averaged for each of the five tryptophans in both structures (2, 4).…”

Protein structure determination from NMR chemical shifts

“…The structural information contained in the chemical shifts is, however, very different in nature from that provided by NOEs, because the latter report on pairwise distances between specific protons and can thus provide unequivocal information about the relative spatial locations of different residues in a protein sequence (1). The chemical shift associated with a specific atom, by contrast, is a summation of many contributing factors (16)(17)(18) so that the reliable identification of interaction partners is very difficult, even though they may be substantially influenced by contacts between residues, such as hydrogen bonding and proximity to aromatic rings, that are at very different locations in the protein sequence. If such effects could be interpreted in depth, therefore, they would enable the characterization of the detailed environment of virtually every atom in the structure and, in turn, the determination of a unique overall conformation compatible with all such environments.…”

Fast and Accurate Predictions of Protein NMR Chemical Shifts from Interatomic Distances

“…This subject has recently been studied intensively, and several methods have become available for this purpose. [5][6][7][8] With such tools it has become possible to search the conformational space of proteins to find structures whose predicted chemical shifts closely match the experimentally measured ones. These developments have led to a series of methods that enable the determination of the structures of proteins and of protein complexes from chemical shifts at a resolution often comparable to that provided by more standard NMR methods.…”