Dynamic Monte Carlo simulations of globular protein folding. Model studies of in vivo assembly of four helix bundles and four member beta-barrels.
Dynamic Monte Carlo simulations of globular protein folding. Model studies of in vivo assembly of four helix bundles and four member beta-barrels.
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球状蛋白质折叠的动态蒙特卡罗模拟。
DOI：
10.1016/s0022-2836(05)80103-2
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发表时间：
1990
影响因子：
5.6
通讯作者：
Skolnick,J
中科院分区：
文献类型：
--
作者：
Sikorski,A;Skolnick,J
作为正在进行的一系列球形蛋白质折叠动态蒙特卡罗模拟的一部分，在高度理想的体内条件下，研究了模型四成员β桶和四螺旋束的折叠途径的性质。核糖体被粗略地模拟成一个惰性的硬壁，模型蛋白链附着在上面。详细讨论了三种情况。第一个过程对应于翻译后组装，在这个过程中，完全合成的链被拴在细胞壁上，并在强变性条件下开始组装。系统被冷却，链条被允许折叠。有趣的是，螺旋图案倾向于与墙壁平行组装，而β-桶则主要以其主轴垂直于墙壁组装。在前一种情况下，主要的中间产物，螺旋发夹，不同于自由溶液中的三螺旋束。墙壁的作用是减少必须搜索的配置空间的扩展，并有助于折叠。还模拟了可能导致共平移折叠的两种情况。在第一种情况下，为了消除壁面效应，在自由溶液中缓慢合成链，在第二种情况下，从壁面缓慢合成链。在所有情况下，观察到链在翻译后折叠。虽然在合成过程中观察到部分折叠的中间体，但它们缺乏稳定性，无法存活到链合成完成。讨论了这些结果对真实蛋白质链体内折叠的意义，并提出了一个多结构域蛋白质折叠模型。
As part of an ongoing series of dynamic Monte Carlo simulations of globular protein folding, the nature of the folding pathway, of model four-memberβ-barrels and four-helix bundles, under highly idealized conditionsin vivo, has been examined. The ribosome is crudely modeled as an inert hard wall on to which the model protein chain is attached. Three cases are considered in detail. The first corresponds to post-translational assembly in which the fully synthesized chain is tethered to the wall and starts out under strongly denaturing conditions. The system is cooled down, and the chain is allowed to fold. Interestingly, the helical motif prefers to assemble parallel to the wall, whereas theβ-barrel, predominantly assembles with its principal axis perpendicular to the wall. In the former case, the dominant intermediate, the helical hairpin, is different from that in free solution, a three-helix bundle. The wall acts to reduce the expanse of configuration space that must be searched and aids in folding. Two situations that might lead to co-translational folding are also simulated. In the first case, to eliminate wall effects, the chain is slowly synthesized in free solution, and in the second case, it is slowly synthesized from the wall. In all cases, the chains are observed to fold post-translationally. While partially folded intermediates are observed during synthesis, they lack the stability to survive until chain synthesis is complete. The implications of these results for the foldingin vivoof real protein chains is discussed, and a model of multiple domain protein folding is proposed.