[1P-20*] Design rules of the register shift of the βαβmotif in protein structures: A database analysis and computational verification
The β sheet register shift, which is the shift at the end of a β strand between spatially adjacent β strands, is an important quantity for de novo protein design, because it must be specified by researchers manually in the initial stage of de novo design of a β sheet proteins. Although this is a necessary step, the design rules regarding the types of register shift that are physically possible remain unknown. In this paper, we proposed design rules for the register shift in the β-α-β motif. By analyzing a protein structure database, we discovered empirical rules for the register shift of the β-α and α-β loops in the β-α-β motif. We found that (1) there is asymmetry in the register shift, i.e., the negative register shift is very small in the database; and (2) the frequent/infrequent register shift varies. Next, we conducted a computational exhausitive structural search and selected only the conformations that satisfied the exclusion volume condition and hydrogen-bond satisfaction, which revealed that the empirical rule deduced from the database analysis can be explained by physical factors. These design rules may be useful as a guideline for specifying designable blueprints for the de novo design of proteins containing a β-α-β motif.