Speeding molecular recognition by using the folding funnel: The fly-casting mechanism
Speeding molecular recognition by using the folding funnel: The fly-casting mechanism
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DOI：
10.1073/pnas.160259697
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发表时间：
2000-08-01
影响因子：
11.1
通讯作者：
Wolynes, PG
中科院分区：
文献类型：
--
作者：
Shoemaker, BA;Portman, JJ;Wolynes, PG
蛋白质的折叠和结合是相似的过程，细胞中的许多蛋白质都是展开的，因此折叠和功能是耦合的。本文研究了蛋白质折叠对结合动力学的影响，我们发现相对非结构化的蛋白质分子比折叠态具有更大的特定结合位点捕获半径，其构象自由受到限制。在这种结合情况下，未折叠的状态在相对较大的距离上结合较弱，然后随着蛋白质接近结合位点而折叠：“飞投机制”。我们用假设的将单个抑制因子分子结合到DNA位点的动力学来说明这种情况，并发现结合率可以显著提高，而不是完全折叠的蛋白质的结合率。
Protein folding and binding are kindred processes, Many proteins in the cell are unfolded, so folding and function are coupled. This paper investigates how binding kinetics is influenced by the folding of a protein, We find that a relatively unstructured protein molecule can have a greater capture radius for a specific binding site than the folded state with its restricted conformational freedom. In this scenario of binding, the unfolded state binds weakly at a relatively large distance followed by folding as the protein approaches the binding site: the "fly-casting mechanism." We illustrate this scenario with the hypothetical kinetics of binding a single repressor molecule to a DNA site and find that the binding rate can be significantly enhanced over the rate of binding of a fully folded protein.