Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH, 8093 Zrich, Switzerland.
J Am Chem Soc. 2010 Jun 2;132(21):7276-8. doi: 10.1021/ja100879k.
Computer simulation using long molecular dynamics (MD) can be used to simulate the folding equilibria of peptides and small proteins. However, a systematic investigation of the influence of the side-chain composition and position at the backbone on the folding equilibrium is computationally as well as experimentally too expensive because of the exponentially growing number of possible side-chain compositions and combinations along the peptide chain. Here, we show that application of the one-step perturbation technique may solve this problem, at least computationally; that is, one can predict many folding equilibria of a polypeptide with different side-chain substitutions from just one single MD simulation using an unphysical reference state. The methodology reduces the number of required separate simulations by an order of magnitude.
使用长分子动力学（MD）的计算机模拟可用于模拟肽和小蛋白的折叠平衡。然而，由于沿肽链的侧链组成和位置对折叠平衡的系统研究在计算和实验上都过于昂贵，因为可能的侧链组成和组合呈指数增长。在这里，我们表明，一步扰动技术的应用至少在计算上可以解决这个问题；也就是说，可以仅使用一个不合理的参考状态，从单个 MD 模拟中预测具有不同侧链取代的多肽的许多折叠平衡。该方法将所需的单独模拟数量减少了一个数量级。
