Models for excluded volume interaction between an unfolded protein and rigid macromolecular cosolutes: Macromolecular crowding and protein stability revisited
Models for excluded volume interaction between an unfolded protein and rigid macromolecular cosolutes: Macromolecular crowding and protein stability revisited
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DOI：
10.1529/biophysj.104.050351
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发表时间：
2005-02-01
影响因子：
3.4
通讯作者：
Minton, AP
中科院分区：
文献类型：
--
作者：
Minton, AP
提出了未折叠多肽链与硬球或硬棒共质之间排除体积相互作用的统计热力学模型，允许估计具有固定回转半径的多肽链从稀（理想）溶液到含有任一共质体积分数 phi 的溶液转移的自由能。还提出了蛋白质的独特天然状态和多种未折叠或部分未折叠状态之间平衡的一般热力学描述，通过它们各自的回转半径来区分。与 Goldenberg 于 2003 年发表的四种不同未折叠蛋白质的回转半径分布的蒙特卡罗计算结果一起，这些模型用于估计分子间排除体积对四种蛋白质各自的天然和非天然构象之间平衡的实验可测量的表观二态常数的影响，以及对未折叠蛋白质的实验可测量的均方根回转半径的影响。模型计算预测，添加体积分数超过 0.1 的惰性共溶质可以稳定相对于未折叠状态的天然状态，稳定量随着 phi 以及天然蛋白质相对于惰性共溶质大小的大小而强烈增加，并导致多种未折叠状态的显着压缩。预测效果与多项已发表的实验研究的结果定性和/或半定量一致。
Statistical-thermodynamic models for the excluded volume interaction between an unfolded polypeptide chain and a hard sphere or hard rod cosolute are presented, permitting estimation of the free energy of transfer of a polypeptide chain with fixed radius of gyration from a dilute (ideal) solution to a solution containing volume fraction phi of either cosolute. Also presented is a general thermodynamic description of the equilibrium between a unique native state and a manifold of unfolded or partially unfolded states of a protein distinguished by their respective radii of gyration. Together with results of a Monte Carlo calculation of the distribution of radii of gyration of four different unfolded proteins published by Goldenberg in 2003, these models are used to estimate the effect of intermolecular excluded volume upon an experimentally measurable apparent two-state constant for equilibrium between native and nonnative conformations of each of the four proteins, and upon the experimentally measurable root mean-square radius of gyration of the unfolded protein. Model calculations predict that addition of inert cosolutes at volume fractions exceeding 0.1 stabilizes the native state relative to unfolded states by an amount that increases strongly with phi and with the size of the native protein relative to the size of inert cosolute, and results in significant compaction of the manifold of unfolded states. Predicted effects are in qualitative and/or semiquantitative accord with the results of several published experimental studies.