Calculation of the free energy and cooperativity of protein folding.
Calculation of the free energy and cooperativity of protein folding.
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DOI：
10.1371/journal.pone.0000446
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发表时间：
2007-05-16
期刊：
影响因子：
3.7
通讯作者：
Osman R
中科院分区：
文献类型：
--
作者：
Kentsis A;Gindin T;Mezei M;Osman R
蛋白质折叠自由能的计算和预组装的描绘对于理解、预测和设计生物大分子具有重要意义。在这里，我们介绍了一种能量平滑的并行回火副本交换蒙特卡罗(REMS)变种，它允许在分子水化条件下对柔性溶质进行有效的构型采样。用它计算了模型球状蛋白质Trp Cage TC5b的热稳定性，得到了与实验测量很好的一致。我们发现TC5b的稳定性是通过局域和非局域相互作用的耦合形成的。值得注意的是，这些结构中的许多在高温下持续存在，伴随着类自然组态和介态的起源，否则处于宏观无序的展开状态。图形流形学习揭示了这些介态到本征状态的转换在结构上是异质的，它们形成的协作性很大程度上是由展开态系综编码的。总之，这些研究建立了这个模型球状蛋白折叠的热力学和结构预组织的程度，并实现了从头计算大分子稳定性，这是从头计算结构预测、基因组注释和药物设计所需的。
Calculation of the free energy of protein folding and delineation of its pre-organization are of foremost importance for understanding, predicting and designing biological macromolecules. Here, we introduce an energy smoothing variant of parallel tempering replica exchange Monte Carlo (REMS) that allows for efficient configurational sampling of flexible solutes under the conditions of molecular hydration. Its usage to calculate the thermal stability of a model globular protein, Trp cage TC5b, achieves excellent agreement with experimental measurements. We find that the stability of TC5b is attained through the coupled formation of local and non-local interactions. Remarkably, many of these structures persist at high temperature, concomitant with the origin of native-like configurations and mesostates in an otherwise macroscopically disordered unfolded state. Graph manifold learning reveals that the conversion of these mesostates to the native state is structurally heterogeneous, and that the cooperativity of their formation is encoded largely by the unfolded state ensemble. In all, these studies establish the extent of thermodynamic and structural pre-organization of folding of this model globular protein, and achieve the calculation of macromolecular stability ab initio, as required for ab initio structure prediction, genome annotation, and drug design.
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影响因子：
13.8
作者：
Baldwin, RL;Rose, GD
通讯作者：
Rose, GD
影响因子：
2.8
作者：
Hansmann, UHE
通讯作者：
Hansmann, UHE
影响因子：
56.9
作者：
Klein-Seetharaman, J;Oikawa, M;Schwalbe, H
通讯作者：
Schwalbe, H
影响因子：
2.9
作者：
KARPEN, ME;TOBIAS, DJ;BROOKS, CL
通讯作者：
BROOKS, CL
DOI：
10.1080/01621459.1995.10476590
发表时间：
1995-09-01
影响因子：
3.7
作者：
GEYER, CJ;THOMPSON, EA
通讯作者：
THOMPSON, EA