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[摘要]：The ability to design well-folding beta-peptides with a specific biological activity requires detailed insight into the relationship between the beta-amino acid sequence and the three-dimensional structure of the peptide. Here, we present a molecular-dynamics (MD) study of the influence of a variation of a side chain on the folding equilibrium of a beta-heptapeptide that folds into a 3(14)-helical structure. The side chain of the 5th residue, a valine, was changed into five differently branched side chains of different lengths and polarity, Ala, Leu, Ile, Ser, and Thr. Two computational techniques, long-time MD simulations and the one-step perturbation method, were used to obtain free enthalpies of folding. The simulations show that all six peptides exhibit similar folding behavior, and that their dominant fold is the same, i.e., a 3(14)-helix. Despite the similarities of their structural properties, a small stabilization effect of ca. 2 kJ mol(-1) on the folding equilibrium of the 3(14)-helical structure due to a branching C-gamma-atom in the beta(3)-side chain is observed. These results confirm those of previous circular dichroism (CD) studies. The length of side chain and its polarity seem to have no apparent (de)stabilization effect. Application of the cost-effective one-step perturbation method to predict free-enthalpy differences appeared to yield an overall accuracy of about k(B)T, which is not sufficient to detect the small stabilization effect. |
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