Clementi Cecilia, Plotkin Steven S
Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, USA.
Protein Sci. 2004 Jul;13(7):1750-66. doi: 10.1110/ps.03580104.
Proteins are minimally frustrated polymers. However, for realistic protein models, nonnative interactions must be taken into account. In this paper, we analyze the effect of nonnative interactions on the folding rate and on the folding free energy barrier. We present an analytic theory to account for the modification on the free energy landscape upon introduction of nonnative contacts, added as a perturbation to the strong native interactions driving folding. Our theory predicts a rate-enhancement regime at fixed temperature, under the introduction of weak, nonnative interactions. We have thoroughly tested this theoretical prediction with simulations of a coarse-grained protein model, by using an off-lattice C(alpha)model of the src-SH3 domain. The strong agreement between results from simulations and theory confirm the nontrivial result that a relatively small amount of nonnative interaction energy can actually assist the folding to the native structure.
蛋白质是最小受挫聚合物。然而，对于实际的蛋白质模型，必须考虑非天然相互作用。在本文中，我们分析了非天然相互作用对折叠速率和折叠自由能垒的影响。我们提出了一种解析理论，以解释引入非天然接触时自由能景观的变化，这些非天然接触作为对驱动折叠的强天然相互作用的微扰而添加。我们的理论预测，在固定温度下，引入弱非天然相互作用时会出现速率增强机制。我们通过使用src-SH3结构域的非晶格Cα模型，对粗粒化蛋白质模型进行模拟，全面测试了这一理论预测。模拟结果与理论结果之间的高度一致性证实了一个重要结果，即相对少量的非天然相互作用能实际上可以帮助折叠成天然结构。
