Context-Independent, Temperature-Dependent Helical Propensities for Amino Acid Residues

摘要

Assigned from data sets measured in water at 2,25, and 60 ℃ containing ~(13)C=O NMR chemical shifts and [θ]_(222) ellipticities, helical propensities are reported for the 20 genetically coded amino acids, as well as for norvaline and norleucine. These have been introduced by chemical synthesis at central sites within length-optimized, spaced, solubilized Ala_(19) hosts. The resulting polyalanine-derived, quantitative propensity sets express for each residue its temperature-dependent but context-independent tendency to forego a coil state and join a preexisting helical conformation. At 2 ℃ their rank ordering is: P « G < H < C, T, N < S < Y, F, W < V, D < K < Q < I < R, M < L < E < A; at 60 ℃ the rank becomes: H, P < G < C < R, K < T, Y, F < N, V < S < Q < W, D < I, M < E < A < L. The AAG values, kcal/mol, relative to alanine, for the cluster T, N, S, Y, F, W, V, D, Q, imply that at 2 ℃ all are strong breakers: ΔΔG_(mean)n = +0.63 ± 0.11, but at 60 ℃ their breaking tendencies are dramatically attenuated and converge toward the mean: ΔΔG_(mean) = +0.25 ± 0,07. Accurate modeling of helix-rich proteins found in thermophiles, mesophiles, and organisms that flourish near 0 ℃ thus requires appropriately matched propensity sets. Comparisons are offered between the temperature-dependent propensity assignments of this study and those previously assigned by the Scheraga group; the special problems that attend propensity assignments for charged residues are illustrated by lysine guest data; and comparisons of errors in helicity assignments from shifts and ellipticity data show that the former provide superior precision and accuracy.