Microsecond simulations of the folding/unfolding thermodynamics of the Trp-cage miniprotein.
Microsecond simulations of the folding/unfolding thermodynamics of the Trp-cage miniprotein.
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DOI：
10.1002/prot.22702
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发表时间：
2010-06
影响因子：
2.9
通讯作者：
Garcia, Angel E.
中科院分区：
文献类型：
--
作者：
Day, Ryan;Paschek, Dietmar;Garcia, Angel E.
我们利用Amberff99Sb力场对Trp-Cage迷你蛋白在显性溶剂中的全原子模型进行了详细的分子动力学模拟，研究了Trp-Cage迷你蛋白的无偏折叠/去折叠热力学。副本交换分子动力学(REMD)模拟被用来在涵盖折叠和未折叠状态的广泛温度范围内以及在两种密度下对蛋白质系综进行采样。得到的系综在每个副本的1μS时间标度内达到平衡。计算所用的总模拟时间超过100μS，使用折叠分数、压力以及折叠和未折叠状态之间的能量差作为温度的函数的系综平均值来模拟整个模拟中采样的温度和压力区域的折叠转变的自由能ΔG(P，T)。ΔG(P，T)图描述了在采样的温度和压力范围内的椭圆，预测体系在低温和高压下可以经历压力诱导的展开和冷变性，在低压和高温下可以展开。计算得到的自由能函数与实验测得的折叠转变温度(Tf=321K)、自由能和比热变化有很好的一致性。然而，热焓和熵的变化与实验值有很大不同。我们推测，这些差异可能是由于模拟中使用的半经验力场的简单性，可能需要更精细的力场来适当地描述蛋白质的热力学。
We study the unbiased folding/unfolding thermodynamics of the Trp-cage miniprotein using detailed molecular dynamics simulations of an all-atom model of the protein in explicit solvent, using the Amberff99SB force field. Replica-exchange molecular dynamics (REMD) simulations are used to sample the protein ensembles over a broad range of temperatures covering the folded and unfolded states, and at two densities. The obtained ensembles are shown to reach equilibrium in the 1 μs per replica timescale. The total simulation time employed in the calculations exceeds 100 μs. Ensemble averages of the fraction folded, pressure, and energy differences between the folded and unfolded states as a function of temperature are used to model the free energy of the folding transition, ΔG(P,T), over the whole region of temperature and pressures sampled in the simulations. The ΔG(P,T) diagram describes an ellipse over the range of temperatures and pressures sampled, predicting that the system can undergo pressure induced unfolding and cold denaturation at low temperatures and high pressures, and unfolding at low pressures and high temperatures. The calculated free energy function exhibits remarkably good agreement with the experimental folding transition temperature (Tf = 321 K), free energy and specific heat changes. However, changes in enthalpy and entropy are significantly different than the experimental values. We speculate that these differences may be due to the simplicity of the semi-empirical force field used in the simulations and that more elaborate force fields may be required to describe appropriately the thermodynamics of proteins.
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影响因子：
2.9
作者：
Kannan, Srinivasaraghavan;Zacharias, Martin
通讯作者：
Zacharias, Martin
影响因子：
2.9
作者：
Hudaky, Peter;Straner, Pal;Perczel, Andras
通讯作者：
Perczel, Andras
DOI：
10.1073/pnas.0402933101
发表时间：
2004-06-22
影响因子：
11.1
作者：
Gnanakaran, S;Hochstrasser, RM;García, AE
通讯作者：
García, AE
影响因子：
4.4
作者：
Ghosh, T;García, AE;Garde, S
通讯作者：
Garde, S
影响因子：
15
作者：
Ghosh, T;García, AE;Garde, S
通讯作者：
Garde, S