INVESTIGADORES
MARTIN Osvaldo Antonio
congresos y reuniones científicas
Título:
CheShift: A protein structure validation method
Autor/es:
VILA, J.A.; ARNAUTOVA Y.A.; MARTIN, O.A.; SCHERAGA H.A.
Lugar:
Quilmes
Reunión:
Congreso; I Congreso Argentino de Bioinformática y Biología Computacional.; 2010
Institución organizadora:
Sociedad Argentina de Bioinformática y Biología Computacional
Resumen:
Background:Quantum-chemical calculation of chemical shifts could be used as a standard validation method for protein structures. 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 torsional angles for all 20 naturally occurring amino acids was generated. Their 13C(alpha) 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, has been developed to predict 13C(alpha) 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 A 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 A. Comparative analysis carried out with 4 popular servers, namely SHIFTS, SHIFTX, SPARTA, and PROSHIFT, for these 3 sets of conformations was carried out.ConclusionCheShift 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 freely available for academic purpose at http://cheshift.com/