Mechanics of forced unfolding of proteins
Mechanics of forced unfolding of proteins
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DOI：
10.1016/j.actbio.2009.01.038
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发表时间：
2009-07-01
影响因子：
9.7
通讯作者：
Purohit, Prashant K.
中科院分区：
文献类型：
--
作者：
Su, Tianxiang;Purohit, Prashant K.
我们描述并求解了蛋白质强制展开的二态动力学模型。蛋白质寡聚物被建模为异质的、自由连接的链，具有两个可能的库恩长度和轮廓长度值，代表其折叠和展开构型。我们获得了不同类型负载条件下蛋白质寡聚物的力延伸响应的解析解。我们将恒速拉力的解析解与泛素和纤维蛋白原的力延伸数据进行拟合，并获得两种蛋白质的模型参数，例如库恩长度和动力学系数。然后，我们预测它们在线性增加的力下的反应，并发现我们的泛素解决方案与一组不同的实验一致。我们的计算表明，低力下蛋白质的重折叠率比解折叠率大几个数量级，忽略它可能会导致对解折叠力的预测较低，尤其是在高拉伸速度下。通过考虑蛋白质的重折叠，我们获得了一个临界力，低于该力，平衡就会偏向于折叠状态。我们的计算还提出了确定过渡态与代表蛋白质折叠和展开状态的能量井的距离的新方法。 (C) 2009 Acta Materialia Inc. 由 Elsevier Ltd 出版。保留所有权利。
We describe and solve a two-state kinetic model for the forced unfolding of proteins. The protein oligomer is modeled as a heterogeneous, freely jointed chain with two possible values of Kuhn length and contour length representing its folded and unfolded configurations. We obtain analytical solutions for the force-extension response of the protein oligomer for different types of loading conditions. We fit the analytical solutions for constant-velocity pulling to the force-extension data for ubiquitin and fibrinogen and obtain model parameters, such as Kuhn lengths and kinetic coefficients, for both proteins. We then predict their response under a linearly increasing force and find that our solutions for ubiquitin are consistent with a different set of experiments. Our calculations suggest that the refolding rate of proteins at low forces is several orders larger than the unfolding rate, and neglecting it can lead to lower predictions for the unfolding force, especially at high stretching velocities. By accounting for the refolding of proteins we obtain a critical force below which equilibrium is biased in favor of the folded state. Our calculations also suggest new methods to determine the distance of the transition state from the energy wells representing the folded and unfolded states of a protein. (C) 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.