Temperature and pressure denaturation of chignolin: Folding and unfolding simulation by multibaric-multithermal molecular dynamics method
Temperature and pressure denaturation of chignolin: Folding and unfolding simulation by multibaric-multithermal molecular dynamics method
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DOI：
10.1002/prot.24125
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发表时间：
2012-10-01
影响因子：
2.9
通讯作者：
Okumura, Hisashi
中科院分区：
文献类型：
--
作者：
Okumura, Hisashi
采用分子动力学（MD）方法对一种含有10个残基的蛋白质--蛋白质采用Amber parm 99 SB力场的全原子模型，水分子采用TIP 3 P模型。该MD模拟涵盖了260至560 K之间的温度和0.1至600 MPa之间的压力范围，并对许多构象进行了采样，而不会被困在局部最小自由能状态。天然β-发夹结构的折叠事件发生五次，观察到四次解折叠事件。随着温度和/或压力的增加，折叠的姜木酚素的分数减少。偏摩尔焓变？H和偏摩尔体积变化？展开的V计算为？H = 24.1 ± 4.9 kJ/mol; V = -5.6 +/- 1.5 cm3/mol。这些值与最近的实验结果吻合得很好。阐明了典型的局部最小自由能构象，折叠和去折叠途径。当chignolin从β-发夹结构展开时，只有C末端或C和N末端首先打开。它可以经历α-螺旋或310-螺旋结构，并最终展开为延伸结构。并讨论了温度变性和压力变性机理的差异。温度变性是通过使蛋白质转移到更高的熵状态，并使其在更大的空间内移动而引起的。压力变性的原因是水分子接近疏水残基，这些残基在折叠状态下没有很好地水合，并且一些疏水接触被破坏。Proteins 2012;. (C)2012 Wiley Periodicals，Inc.
A multibaric-multithermal molecular dynamics (MD) simulation of a 10-residue protein, chignolin, was performed. All-atom model with the Amber parm99SB force field was used for the protein and the TIP3P model was used for the explicit water molecules. This MD simulation covered wide ranges of temperature between 260 and 560 K and pressure between 0.1 and 600 MPa and sampled many conformations without getting trapped in local-minimum free-energy states. Folding events to the native beta-hairpin structure occurred five times and unfolding events were observed four times. As the temperature and/or pressure increases, fraction of folded chignolin decreases. The partial molar enthalpy change ?H and partial molar volume change ?V of unfolding were calculated as ?H = 24.1 +/- 4.9 kJ/mol and ?V = -5.6 +/- 1.5 cm3/mol, respectively. These values agree well with recent experimental results. Illustrating typical local-minimum free-energy conformations, folding and unfolding pathways were revealed. When chignolin unfolds from the beta-hairpin structure, only the C terminus or both C and N termini open first. It may undergo an a-helix or 310-helix structure and finally unfolds to the extended structure. Difference of the mechanism between temperature denaturation and pressure denaturation is also discussed. Temperature denaturation is caused by making the protein transferred to a higher entropy state and making it move around more with larger space. The reason for pressure denaturation is that water molecules approach the hydrophobic residues, which are not well hydrated at the folded state, and some hydrophobic contacts are broken. Proteins 2012;. (C) 2012 Wiley Periodicals, Inc.