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Titolo:
CHEMICAL-SHIFTS IN PROTEINS - A SHIELDING TRAJECTORY ANALYSIS OF THE FLUORINE NUCLEAR-MAGNETIC-RESONANCE SPECTRUM OF THE ESCHERICHIA-COLI GALACTOSE BINDING-PROTEIN USING A MULTIPOLE SHIELDING POLARIZABILITY LOCAL REACTION FIELD MOLECULAR-DYNAMICS APPROACH
Autore:
PEARSON JG; OLDFIELD E; LEE FS; WARSHEL A;
Indirizzi:
UNIV ILLINOIS,DEPT CHEM,505 S MATHEWS AVE URBANA IL 61801 UNIV ILLINOIS,DEPT CHEM,505 S MATHEWS AVE URBANA IL 61801 UNIV SO CALIF,DEPT CHEM LOS ANGELES CA 90089
Titolo Testata:
Journal of the American Chemical Society
fascicolo: 15, volume: 115, anno: 1993,
pagine: 6851 - 6862
SICI:
0002-7863(1993)115:15<6851:CIP-AS>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
D-LACTATE DEHYDROGENASE; FLUOROTYROSINE ALKALINE-PHOSPHATASE; F-19 NMR; CHEMOSENSORY RECEPTOR; DIHYDROFOLATE-REDUCTASE; SALMONELLA-TYPHIMURIUM; SOLVATED PROTEINS; STRUCTURAL-CHANGE; ELECTRIC-FIELD; HEME-PROTEINS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
87
Recensione:
Indirizzi per estratti:
Citazione:
J.G. Pearson et al., "CHEMICAL-SHIFTS IN PROTEINS - A SHIELDING TRAJECTORY ANALYSIS OF THE FLUORINE NUCLEAR-MAGNETIC-RESONANCE SPECTRUM OF THE ESCHERICHIA-COLI GALACTOSE BINDING-PROTEIN USING A MULTIPOLE SHIELDING POLARIZABILITY LOCAL REACTION FIELD MOLECULAR-DYNAMICS APPROACH", Journal of the American Chemical Society, 115(15), 1993, pp. 6851-6862

Abstract

We report the first successful calculation of the fluorine nuclear magnetic resonance spectrum of a protein, the galactose binding protein from Escherichia coli, labeled with [5-F-19]tryptophan. Our results indicate that the experimental F-19 chemical shifts are dominated by weak, or long-range, electrical interactions, which can be calculated by using the responses of the shielding tensor elements to the uniform field components (partial derivative sigma(alphabeta)/partial derivativeE(x)) and the nonuniform or gradient terms (partial derivative sigma(alphabeta)/partial derivative V(ii)), together with the average valuesof the fields (E(x)) and field gradients (V(ii)) obtained from molecular dynamics (MD) trajectories. A series of ''shielding trajectories'', DELTAsigma(E(x), V(xx), V(yy), V(zz)) f(tau), are obtained, and the mean values, DELTAsigmaBAR, correlate well with the actual shift pattern and overall shift range observed experimentally (Luck, L. A.; Falke, J. J. Biochemistry 1991, 30, 4248-4256). The computed F-19 NMR shielding of the pentapeptide Gly-Gly-[5-F]Trp-Gly-Gly in H2O is close to, but somewhat more shielded than, that of the denatured protein. Almostall computed F-19 chemical shifts are upfield of the field-free value, in accord with the results of ab initio calculations. The chemical shifts calculated are sensitive to the charge chosen for F in the LRF-MD trajectories, and best agreement with experiment is obtained with q(F) = -0.25. Calculations on the Salmonella typhimurium galactose binding protein yield extremely similar chemical shift spectra, consistent with the approximately 7% difference in amino acid composition. The uniform field components make the largest contributions to the shieldingpatterns observed, presumably because the gradient terms fall off more rapidly with distance. The exposed residue, Trp 284, has the largestamplitude of fluctuation associated with its shielding trajectory, possibly due to the rapid and random movement of neighboring water molecules. Trp 284 is highly shielded due to interaction with water, although other buried residues (e.g. Trp 133) may also be highly shielded, due to electric field effects within the protein. Our results imply that van der Waals interactions do not play a major role for fluorine shielding nonequivalence in proteins, since the experimental results can be reproduced by using solely the computed field and field gradient terms. The ability to predict protein NMR shielding patterns and ranges offers promise for structural analysis and also provides a way of validating different methods of computing protein electrostatics. In this respect, it is instructive to note that the charge fields from ionizedsurface groups are found to be largely shielded by the dielectric response of the solvent and the protein.

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Documento generato il 26/11/20 alle ore 19:34:56