A physical basis for protein secondary structure

Abstract

A physical theory of protein secondary structure is proposed and tested by performing exceedingly simple Monte Carlo simulations. In essence, secondary structure propensities are predominantly a consequence of two competing local effects, one favoring hydrogen bond formation in helices and turns, the other opposing the attendant reduction in sidechain conformational entropy on helix and turn formation. These sequence specific biases are densely dispersed throughout the unfolded polypeptide chain, where they serve to preorganize the folding process and largely, but imperfectly, anticipate the native secondary structure.

Figure 1

Histogram of data from Table 2. The statistical bias toward native secondary structure in helix (red), strand (green), turn (blue), and generalized turn (black) for all segments in Table 2 is parceled into bins, with statistical weights that range from 0.0 to 1.0 in increments of 0.1. The height of each bar corresponds to the percentage of segments in the given bin. For example, 19% of all native helices in the total set of proteins have statistical weights between 0.5 and 0.6 in these simulations, as indicated by the red bar in bin 0.5–0.6. Data for generalized turns are the sum of their turn and helix percentages.