Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH, Zürich, Switzerland.
J Phys Chem B. 2011 Nov 10;115(44):12984-92. doi: 10.1021/jp2053508. Epub 2011 Oct 14.
The ability to design well-folding β-peptides with a specific biological activity requires detailed insight into the relationship between the β-amino acid sequence and the dominant three-dimensional structure of such a peptide. To this end, secondary structure preferences of two sets of 16 β-peptides were investigated by means of one-step perturbation using molecular dynamics (MD) simulations. For each set of peptides, two reference-state simulations and one perturbed-state simulation were carried out to predict the secondary structure preferences for the other 15 peptides. The results show that the substitution of a methyl group in the third or fourth residue stabilizes the left-handed 3(14)-helix over the right-handed 2.7(10/12)-helix for the set of hexapeptides A; for the set of heptapeptides B, having methyl substitutions at both β- and α-carbon positions of the fourth or fifth residue stabilizes the left-handed 3(14)-helix over the right-handed 2.5(12)-helix. Not only the side-chain substitution pattern but also the side-chain composition affects the relative stability of different secondary structures. The approach described here may be of use in peptide design with an eye to obtaining peptides with particular folds and biological activities.
设计具有特定生物活性的折叠良好的β-肽的能力需要深入了解β-氨基酸序列与该肽的主要三维结构之间的关系。为此，使用一步扰动的分子动力学 (MD) 模拟研究了两组 16 个 β-肽的二级结构偏好性。对于每组肽，进行了两个参考态模拟和一个扰动态模拟，以预测其他 15 个肽的二级结构偏好性。结果表明，对于六肽 A 组，第三个或第四个残基中的甲基取代稳定了左手 3(14)-螺旋，而不是右手 2.7(10/12)-螺旋；对于七肽 B 组，第四个或第五个残基的β-和α-碳原子位置的甲基取代稳定了左手 3(14)-螺旋，而不是右手 2.5(12)-螺旋。不仅侧链取代模式，而且侧链组成也会影响不同二级结构的相对稳定性。这里描述的方法可能有助于设计具有特定折叠和生物活性的肽。
