Thermodynamics of Deca-alanine Folding in Water.
Thermodynamics of Deca-alanine Folding in Water.
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DOI：
10.1021/ct5002076
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发表时间：
2014-07-08
影响因子：
5.5
通讯作者：
Gumbart, James C.
中科院分区：
文献类型：
--
作者：
Hazel, Anthony;Chipot, Christophe;Gumbart, James C.
多肽和蛋白质折叠动力学的测定对于表征它们在生物系统中的功能至关重要。已经开发了许多计算模型和方法来研究原子水平的结构形成。由于其尺寸小、结构简单，十丙氨酸被用作分子动力学（MD）模拟中的模型系统。使用肽的端到端距离作为反应坐标，对真空中展开的自由能进行了广泛的研究。然而，在明确溶剂存在下进行的研究很少。先前的结果表明水中延伸构象的自由能显着降低，但α-螺旋态仍然明显优于延伸态。尽管在真空中足够，但我们表明端到端距离无法捕获水中十丙氨酸折叠的全部复杂性。使用 α 螺旋含量作为第二反应坐标，我们推导出更具描述性的自由能景观，它揭示了扩展构象中的第二能量最小值，其自由能与 α 螺旋状态相当。平衡模拟证明了水中的延伸态和 α 螺旋态的相对稳定性以及两种态之间的转变。这项工作揭示了确定适当的反应坐标以充分表征给定过程的必要性和挑战。
The determination of the folding dynamics of polypeptides and proteins is critical in characterizing their functions in biological systems. Numerous computational models and methods have been developed for studying structure formation at the atomic level. Due to its small size and simple structure, deca-alanine is used as a model system in molecular dynamics (MD) simulations. The free energy of unfolding in vacuum has been studied extensively using the end-to-end distance of the peptide as the reaction coordinate. However, few studies have been conducted in the presence of explicit solvent. Previous results show a significant decrease in the free energy of extended conformations in water, but the α-helical state is still notably favored over the extended state. Although sufficient in vacuum, we show that end-to-end distance is incapable of capturing the full complexity of deca-alanine folding in water. Using α-helical content as a second reaction coordinate, we deduce a more descriptive free-energy landscape, one which reveals a second energy minimum in the extended conformations that is of comparable free energy to the α-helical state. Equilibrium simulations demonstrate the relative stability of the extended and α-helical states in water as well as the transition between the two states. This work reveals both the necessity and challenge of determining a proper reaction coordinate to fully characterize a given process.
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影响因子：
4.4
作者：
Chipot, C;Hénin, J
通讯作者：
Hénin, J
影响因子：
13.8
作者：
Baldwin, RL;Rose, GD
通讯作者：
Rose, GD
影响因子：
3.4
作者：
Best, Robert B.;Buchete, Nicolae-Viorel;Hummer, Gerhard
通讯作者：
Hummer, Gerhard
影响因子：
13.8
作者：
Baldwin, RL;Rose, GD
通讯作者：
Rose, GD
DOI：
10.1073/pnas.100127697
发表时间：
2000-05-23
影响因子：
11.1
作者：
Bolhuis, PG;Dellago, C;Chandler, D
通讯作者：
Chandler, D