Entropy change for free polypeptide chain upon hydrogen bonding

Formation probabilities of different hydrogen bonds between carbonyl oxygen and amide hydrogen were determined by Monte Carlo simulations using a comp uter model in the space of sterically allowable conformations of alanine an d glycine oligopeptides, and the corresponding entropy losses for the pepti de backbone, T DeltaS, were calculated. The model was studied at different criteria of steric interactions. Comparison with the data of other authors showed the values of T DeltaS to be mainly determined by overall extent and type of the state space and to be only slightly dependent on its energy pr ofile. Both short-range and long-range steric interactions were shown to pr event hydrogen bonding, especially in alanine peptides. In the model studie d, the initiation of alpha (R)-helices is associated with T DeltaS = 8-10 k T, and prior formation of a 3/10-turn or one three-center U-bond does not a ppreciably decrease this entropy barrier. Elongation of the alpha (R)-helix by one residue lends to T DeltaS = 3.0-3.7 kT, the helices begin to stabil ize after at least three sequential W-bonds are formed. The difference in t he 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 a ssuming that factors different from helical H-bonds take part in the stabil ization 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 pept ide loop, while the elongation of alpha (R)-helices in the supersecondary h elix-loop-helix structure is favorable as long as the loop conformation rem ains nearly optimal.