Quantum-Mechanics-Derived 13C(alpha); Chemical Shift Server (CheShift) for Protein Structure Validation

VILA J.A.; ARNAUTOVA Y.A.; MARTÍN OSVALDO A.; SCHERAGA H.A.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Año: 2009 p. 16972 - 16977

0027-8424

A server (CheShift) has been developed to predict 13C(alpha) chemical shifts of protein structures. It is based on the generation of 696,916 conformations as a function of the phi,psi,omega,chi1 and chi2 torsional angles for all 20 naturally occurring amino acids. Their 13C(alpha) chemical shifts were computed at the DFT level of theory with a small basis set and extrapolated, with an empirically-determined linear regression formula, to reproduce the values obtained with a larger basis set. Analysis of the accuracy and sensitivity of the CheShift predictions, in terms of both the correlation coefficient R and the conformational-averaged rmsd between the observed and predicted 13C(alpha) chemical shifts, was carried out for three sets of conformations: (a) 36 X-ray-derived protein structures solved at 2.3 Å, or better, resolution, for which sets of 13C(alpha) chemical shifts were available; (b) 15 pairs of X-ray and NMR-derived sets of protein conformations; and (c) a set of decoys for three proteins showing an rmsd with respect to the X-ray structure from which they were derived, of up to 3 Å. Comparative analysis carried out with four popular servers, namely SHIFTS, SHIFTX, SPARTA, and PROSHIFT, for these three sets of conformations demonstrated that CheShift is the most sensitive server with which to detect subtle differences between protein models and, hence, to validate protein structures determined by either X-ray or NMR methods, if the observed 13C(alpha) chemical shifts are available. CheShift is available as a web server at http://cheshift.com.