Hidden complexity of free energy surfaces for peptide (protein) folding
Hidden complexity of free energy surfaces for peptide (protein) folding
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DOI：
10.1073/pnas.0406234101
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发表时间：
2004-10-12
影响因子：
11.1
通讯作者：
Karplus, M
中科院分区：
文献类型：
--
作者：
Krivov, SV;Karplus, M
要了解蛋白质折叠的热力学和动力学，就必须了解控制多肽链运动的自由能面。由于涉及到许多自由度，在描述折叠反应时通常只使用在一个或两个进程变量上的投影曲面。这样的投影会产生相对光滑的表面，但它们可能掩盖了未投影表面的复杂性。本文介绍了一种确定实际（非投影）自由能表面的方法，并将其应用于蛋白质G的第二个β发夹，该发夹已被用作蛋白质折叠的模型系统。该曲面由由长平衡折叠-展开轨迹计算的断连图表示。发现变性态有多个低自由能盆地。然而，多肽在向原生盆地的折叠过程中表现出指数动力学。从目前的分析得到的投影表面有一个简单的形式，与其他研究的β发夹一致。发夹表面隐藏的复杂性表明，蛋白质折叠的标准漏斗图应该重新审视。
An understanding of the thermodynamics and kinetics of protein folding requires a knowledge of the free energy surface governing the motion of the polypeptide chain. Because of the many degrees of freedom involved, surfaces projected on only one or two progress variables are generally used in descriptions of the folding reaction. Such projections result in relatively smooth surfaces, but they could mask the complexity of the unprojected surface. Here we introduce an approach to determine the actual (unprojected) free energy surface and apply it to the second beta-hairpin of protein G, which has been used as a model system for protein folding. The surface is represented by a disconnectivity graph calculated from a long equilibrium folding-unfolding trajectory. The denatured state is found to have multiple low free energy basins. Nevertheless, the peptide shows exponential kinetics in folding to the native basin. Projected surfaces obtained from the present analysis have a simple form in agreement with other studies of the beta-hairpin. The hidden complexity found for the beta-hairpin surface suggests that the standard funnel picture of protein folding should be revisited.