Automated 1H and 13C chemical shift prediction using the BioMagResBank

A computer program has been developed to accurately and automatically predict the ¹H and ¹³C 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 unassigned protein against the BioMagResBank – a public database containing sequences and NMR chemical shifts of nearly 200 assigned proteins Seavey et al. (1991) J. Biomol. NMR, 1, 217–236]. From this initial sequence alignment, the program uses a simple set of rules to directly assign or transfer a complete set of ¹H or ¹³C chemical shifts (from the previously assigned homologues) to the unassigned protein. This homologous assignment protocol takes advantage of the simple fact that homologous proteins tend to share both structural similarity and chemical shift similarity. SHIFTY has been extensively tested on more than 25 medium-sized proteins. Under favorable circumstances, this program can predict the ¹H or ¹³C chemical shifts of proteins with an accuracy far exceeding any other method published to date. With the expo- nential 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.