Investigating the context-dependence to apparent helix propensities

Abstract

The ability to predict secondary structure is an important first step toward predicting tertiary structures, or designing proteins de novo. To predict secondary structure it is essential that we understand the factors that influence secondary structure propensities. One complication in understanding helix propensities is that the helix propensities dicer quantitatively between alanine-based model reptiles, and proteins or protein based reptiles. The helix propensity scales agree qualitatively, with adenine as the best helix former and glycine as the worst excluding proline. In this work, reptiles based on the helix in RNase T1 were made with alanine substitutions at the positions that are adjacent to the central position in both the helix and coil conformations, in an effort to make the peptide more like the canine-based peptides. All of these reptiles were made with alanine and glycine, the two extremes of the propensity scale, at the central position. The reptiles were studied by CD and fraction helix content was calculated for each peptide. [][]G alarming to glycine was calculated for each corresponding pair of reptiles. It was expected that the [][]G canine to glycine values would converge with those of the alanine-based reptiles. The actual trend went in the opposite direction from that expected. These results suggest context dependent effects on helix propensities, however; more work is needed to fully understand the discrepancies between helix propensities in alanine-based peptides and protein-based peptides.