[Change in entropy of the free polypeptide chain during formation of hydrogen bonds].
Formation probabilities of different hydrogen bonds between carbonyl oxygen and amide hydrogen were determined by Monte Carlo simulations using a computer model in the space of sterically allowable conformations of alanine and glycine oligopeptides, and the corresponding entropy losses for the peptide backbone, T delta S, were calculated. The model was studied at different criteria of steric interactions. Comparison with the data of other authors showed the values of T delta S to be mainly determined by overall extent and type of the state space and to be only slightly dependent on its energy profile. Both short-range and long-range steric interactions were shown to prevent hydrogen bonding, especially in alanine peptides. In the model studied, the initiation of alpha(R)-helices is associated with T delta S = 8-10 kT, and prior formation of a 3/10-turn or one three-center H-bond does not appreciably decrease this entropy barrier. Elongation of the alpha(R)-helix by one residue leads to T delta S = 3.0-3.7 kT, the helices begin to stabilize after at least three sequential H-bonds are formed. The difference in the probability of insertion of Ala and Gly into the helix is lower than it follows from comparison of their mobility. The results could be explained assuming that factors different from helical H-bonds take part in the stabilization of the helices. One may suppose upon modeling of folding that even three sequential H-bonds are unable to fix the structure of a flexible peptide loop, while the elongation of alpha(R)-helices in the supersecondary helix-loop-helix structure is favorable as long as the loop conformation remains nearly optimal.