CONICET | Buscador de Institutos y Recursos Humanos

&amp;lt;!-- @page { margin: 2cm } P { margin-bottom: 0.21cm } A:link { color: #0000ff } --&amp;gt;  Background Quantum-chemical calculation of chemical shifts could be used as a standard validation method for protein structures[1]. The high computational cost had hampered the wide use of this tool by the crystallographers and spectroscopicst community. Methods A set of 696,916 conformations as a function of the f, y, w, c1and c2 torsional angles for all 20 naturally occurring amino acids was generated. Their 13Ca chemical shifts were computed at the DFT (Density Functional Theory) 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. Results A web server, CheShift [2]⁠, has been developed to predict 13Ca chemical shifts of protein structures. Analysis of the accuracy and sensitivity of the CheShift predictions, was carried out for 3 sets of conformations: (i) 36 X-ray-derived protein structures solved at 2.3 Å or better resolution (ii) 15 pairs of X-ray and NMR (Nuclear Magnetic Resonance) derived sets of protein conformations; and (iii) a set of decoys for 3 proteins showing an rmsd (root mean square deviation) with respect to the X-ray structure from which they were derived of up to 3 Å. Comparative analysis carried out with 4 popular servers, namely SHIFTS[3, 4]⁠ ,SHIFTX [5]⁠, SPARTA [6]⁠, and PROSHIFT [7]⁠, for these 3 sets of conformations was carried out. Conclusion 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 13Ca chemical shifts are available. CheShift is freely available for academic purpose at http://cheshift.com/