Monte Carlo simulations of the folding of beta-barrel globular proteins.
Monte Carlo simulations of the folding of beta-barrel globular proteins.
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β-桶球状蛋白折叠的蒙特卡罗模拟。
DOI：
10.1073/pnas.85.14.5057
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发表时间：
1988
影响因子：
11.1
通讯作者：
Yaris,R
中科院分区：
文献类型：
--
作者：
Skolnick,J;Kolinski,A;Yaris,R
利用动态蒙特卡罗模拟，研究了模型球状蛋白质从无规卷曲变性态向结构独特的四元β-桶自然态崩塌的必要条件。这些系统可以自由地在所有配置空间中漫游--允许本机和非本机交互。研究了疏水和亲水相互作用的相对重要性以及形成独特自然状态的统计弯曲形成区域的存在或不存在，并探索了从变性到自然(反之亦然)构象转变的必要条件，这种构象转变在热力学上要么全有要么没有，并且总是导致塌缩成相同的四元β-桶。这些条件被发现是疏水/亲水残基的一般模式，允许天然状态区分蛋白质的内部和外部，以及至少对转弯形成是中性的区域的存在。前一组相互作用似乎定义了β拉伸的平均长度，而后一组作用是将本征态锁定在最低自由能状态，即本征构象。这些折叠模拟有力地表明，蛋白质折叠的一般规则是相当稳健的，特定位置的三级相互作用只涉及结构微调。从一系列最初在能量上非常接近的坍塌构象形成结构独特的自然状态所需的条件，高度暗示了一种通过随机突变进行蛋白质进化的机制。这些折叠研究对这种机制的意义进行了定性的探索。
With the use of dynamic Monte Carlo simulations, the necessary conditions for the collapse from a random-coil denatured state to a structurally unique four-member beta-barrel native state of a model globular protein have been investigated. These systems are free to roam through all of configuration space--both native and nonnative interactions are allowed. The relative importance of hydrophobic and hydrophilic interactions and the presence or absence of statistical bend-forming regions for the formation of a unique native state are examined, and the conditions necessary for a denatured-to-native (and vice versa) conformational transition that is thermodynamically all-or-none and which always results in collapse to the same, four-member beta-barrel are explored. These conditions are found to be a general pattern of hydrophobic/hydrophilic residues that allows the native state to differentiate the interior from the exterior of the protein and the presence of regions that are, at the very least, neutral toward turn formation. The former set of interactions seems to define the mean length of the beta-stretch, and the latter set serves to lock the native state into the lowest free energy state, the native conformation. These folding simulations strongly suggest that the general rules of protein folding are rather robust and that site-specific tertiary interactions are only involved in structural fine tuning. The conditions required for the formation of a structurally unique native state from a manifold of collapsed conformations that are originally quite close in energy is highly suggestive of a mechanism of protein evolution by means of random mutations. The implications of these folding studies for such a mechanism are qualitatively explored.