Sequential nearest-neighbor effects on computed 13Cα chemical shifts
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To evaluate sequential nearest-neighbor effects on quantum-chemical calculations of 13Cα chemical shifts, we selected the structure of the nucleic acid binding (NAB) protein from the SARS coronavirus determined by NMR in solution (PDB id 2K87). NAB is a 116-residue α/β protein, which contains 9 prolines and has 50% of its residues located in loops and turns. Overall, the results presented here show that sizeable nearest-neighbor effects are seen only for residues preceding proline, where Pro introduces an overestimation, on average, of 1.73 ppm in the computed 13Cα chemical shifts. A new ensemble of 20 conformers representing the NMR structure of the NAB, which was calculated with an input containing backbone torsion angle constraints derived from the theoretical 13Cα chemical shifts as supplementary data to the NOE distance constraints, exhibits very similar topology and comparable agreement with the NOE constraints as the published NMR structure. However, the two structures differ in the patterns of differences between observed and computed 13Cα chemical shifts, Δ ca,i , for the individual residues along the sequence. This indicates that the Δ ca,i -values for the NAB protein are primarily a consequence of the limited sampling by the bundles of 20 conformers used, as in common practice, to represent the two NMR structures, rather than of local flaws in the structures.
KeywordsQuantum-chemical calculation of 13Cα- chemical shifts NMR structures of proteins Sampling of conformation space
This research was supported by grants from the National Institutes of Health (GM-14312, GM-24893), the National Science Foundation (MCB05-41633), and the Joint Center for Structural Genomics (NIH/NIGMS grant U54-GM074898). Support was also received from the CONICET, FONCyT-ANPCyT (PAV 22642-2), and from the Universidad Nacional de San Luis (P-328501), Argentina. P. S. was supported by a fellowship from the Spanish Ministry of Science and Education and by the Skaggs Institute of Chemical Biology. Kurt Wüthrich is the Cecil H. and Ida M. Green Professor of Structural Biology at TSRI. The research was conducted using the resources of a Beowulf-type cluster located at the Baker Laboratory of Chemistry and Chemical Biology, Cornell University, and the resources of Pople, a facility of the National Science Foundation Terascale Computing System at the Pittsburgh Supercomputer Center.
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