AUTOMATED H-1 AND C-13 CHEMICAL-SHIFT PREDICTION USING THE BIOMAGRESBANK

A computer program has been developed to accurately and automatically predict the H-1 and C-13 chemical shifts of unassigned proteins on the basis of sequence homology. The program (called SHIFTY) uses standard sequence alignment techniques to compare the sequence of an unassigne d protein against the BioMagResBank - a public database containing seq uences and NMR chemical shifts of nearly 200 assigned proteins [Seavey et al. (1991) J. Biomol. NMR, 1, 217-236]. From this initial sequence align ment, the program uses a simple set of rules to directly assign or transfer a complete set of H-1 or C-13 chemical shifts (from the p reviously assigned homologues) to the unassigned protein. This 'homolo gous assignment' protocol takes advantage of the simple fact that homo logous proteins tend to share both structural similarity and chemical shift similarity. SHIFTY has been extensively tested on more than 25 m edium-sized proteins. Under favorable circumstances, this program can predict the H-1 or C-13 chemical shifts of proteins with an accuracy f ar exceeding any other method published to date. With the exponential growth in the number of assigned proteins appearing in the literature (now at a rate of more than 150 per year), we believe that SHIFTY may have widespread utility in assigning individual members in families of related proteins, an endeavor that accounts for a growing portion of the protein NMR work being done today.