Uprading the CheShift-2 Server: 13Cb chemical shift predictions in proteins

ALEJANDRO ICAZATTI; OSVALDO A. MARTIN; YELENA A. ARNAUTOVA; HAROLD A SCHERAGA; JORGE A VILA

San Javier - Tucumán

Congreso; XLI Reunión anual de la Sociedad Argentina de Biofísica; 2012

Sociedad Argentina de Biofísica

Since the seminal work of Spera and Bax (1991) the observed 13Cb  chemical shifts (CS) have been used, predominantly, to determine conformational preferences of the backbone of polypeptides chains, although it could also contain very valuable information about side-chain conformational preferences. In order to explore this possibility, we have expanded our CheShift-2 server to include the prediction of the 13Cb  CS of protein structures. This database of the 13Cb  CS, contains ~600,000 conformations, with the torsional angles (f, y) every 10º,   c1, every 30o, and c2, for the most frequently seen rotamers in proteins,  representing the whole Ramachandran map for all 20 naturally occurring amino acids, except Gly. The 13Cb  CS for each of these conformations was computed at the DFT level of theory. Tests of the upgraded CheShift-2 server include: (i) analysis of the sensitivity and specificity of the 13Cb  CS  versus the 13Ca  CS to detect flaws in side-chain conformations and (ii) use of the 13Cb  CS to validate the c1 side-chain torsional angle predictions, obtained from the computed vicinal coupling constant (3Jab) with the Karplus equation, for three different proteins in solution.