School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
Bioinformatics. 2010 Sep 15;26(18):2266-72. doi: 10.1093/bioinformatics/btq412. Epub 2010 Aug 2.
In nature, protein-protein interactions are constantly evolving under various selective pressures. Nonetheless, it is expected that crucial interactions are maintained through compensatory mutations between interacting proteins. Thus, many studies have used evolutionary sequence data to extract such occurrences of correlated mutation. However, this research is confounded by other evolutionary pressures that contribute to sequence covariance, such as common ancestry.
Here, we focus exclusively on the compensatory mutations deriving from physical protein interactions, by performing large-scale computational mutagenesis experiments for >260 protein-protein interfaces. We investigate the potential for co-adaptability present in protein pairs that are always found together in nature (obligate) and those that are occasionally in complex (transient). By modeling each complex both in bound and unbound forms, we find that naturally transient complexes possess greater relative capacity for correlated mutation than obligate complexes, even when differences in interface size are taken into account.
在自然界中，蛋白质-蛋白质相互作用在各种选择压力下不断进化。尽管如此，人们期望关键相互作用通过相互作用的蛋白质之间的补偿突变得以维持。因此，许多研究利用进化序列数据来提取这种相关突变的发生。然而，这项研究受到其他进化压力的干扰，这些压力导致序列协方差，如共同祖先。
在这里，我们专门通过对 >260 个蛋白质-蛋白质界面进行大规模计算诱变实验，研究源自物理蛋白质相互作用的补偿突变。我们研究了在自然界中总是一起出现的蛋白质对（必需的）和偶尔在复合物中出现的蛋白质对（瞬时的）中存在的共适应性的潜力。通过对结合和未结合形式的每个复合物进行建模，我们发现，即使考虑到界面大小的差异，自然瞬时复合物比必需复合物具有更大的相关突变相对能力。
