Shape variation in protein binding pockets and their ligands
Shape variation in protein binding pockets and their ligands
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DOI：
10.1016/j.jmb.2007.01.086
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发表时间：
2007-04-20
影响因子：
5.6
通讯作者：
Thornton, Janet M.
中科院分区：
文献类型：
--
作者：
Kahraman, Abdullah;Morris, Richard J.;Thornton, Janet M.
关于蛋白质结合袋形状的一个常见假设是，它们与可以结合在那里的小配体分子的形状有关。但这一假设在多大程度上是正确的呢？在这里，我们使用最近开发的形状匹配方法来比较蛋白质结合口袋的形状与它们的配体的形状。我们发现，与同一配体结合的口袋在形状上的变化比配体的构象变化所能解释的更大。这表明，一般来说，几何互补不足以驱动分子识别。然而，当只考虑形状和大小时，我们表明结合口袋对其配体的识别能力的很大一部分取决于它的形状。此外，我们观察到配体和蛋白质之间的“缓冲区”或自由空间区域，这导致结合口袋平均比他们结合的配体大三倍。(C)2007爱思唯尔有限公司。保留所有权利。
A common assumption about the shape of protein binding pockets is that they are related to the shape of the small ligand molecules that can bind there. But to what extent is that assumption true? Here we use a recently developed shape matching method to compare the shapes of protein binding pockets to the shapes of their ligands. We find that pockets binding the same ligand show greater variation in their shapes than can be accounted for by the conformational variability of the ligand. This suggests that geometrical complementarity in general is not sufficient to drive molecular recognition. Nevertheless, we show when considering only shape and size that a significant proportion of the recognition power of a binding pocket for its ligand resides in its shape. Additionally, we observe a "buffer zone" or a region of free space between the ligand and protein, which results in binding pockets being on average three times larger than the ligand that they bind. (c) 2007 Elsevier Ltd. All rights reserved.