School of Life Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China (USTC), Hefei, Anhui 230027, People's Republic of China.
Phys Chem Chem Phys. 2010 Dec 21;12(47):15442-7. doi: 10.1039/c0cp00833h. Epub 2010 Oct 29.
The one-step perturbation technique is used to predict the folding equilibria for 16 peptides with different stereochemical side-chain substitutions through one or two long-time simulations, one of an unphysical reference state and another of one of the 16 peptides for which many folding events can be sampled. The accuracy of the one-step perturbation results was investigated by comparing to results available from long-time MD simulations of particular peptides. Their folding free energies were reproduced within statistical accuracy. The one-step perturbation results show that an axial substitution at either the C(α) or the C(β) position destabilizes the 3(14)-helical conformation of the hepta-β-peptide, which is consistent with data inferred from experimental CD spectra. The methodology reduces the number of required separate simulations by an order of magnitude.
一步摄动技术用于通过一个或两个长时间模拟来预测 16 种具有不同立体化学侧链取代的肽的折叠平衡，其中一个是无物理意义的参考状态，另一个是可以对 16 种肽中的一种进行多次折叠事件采样的状态。通过与特定肽的长时间 MD 模拟结果进行比较，研究了一步摄动结果的准确性。它们的折叠自由能在统计精度范围内得到了重现。一步摄动结果表明，在 C(α)或 C(β)位置的轴向取代会使七肽的 3(14)-螺旋构象不稳定，这与从实验 CD 光谱推断的数据一致。该方法将所需的单独模拟数量减少了一个数量级。
