Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
Drug Discov Today. 2009 Dec;14(23-24):1130-5. doi: 10.1016/j.drudis.2009.08.006. Epub 2009 Sep 3.
Given the key roles of integral membrane proteins as transporters and channels, it is necessary to understand their structures and, hence, mechanisms and regulation at the molecular level. Membrane proteins represent approximately 30% of all proteins of currently sequenced genomes. Paradoxically, however, only approximately 2% of crystal structures deposited in the protein data bank are of membrane proteins, and very few of these are at high resolution (better than 2A). The great disparity between our understanding of soluble proteins and our understanding of membrane proteins is because of the practical problems of working with membrane proteins - specifically, difficulties in expression, purification and crystallization. Thus, computational modeling has been utilized extensively to make crucial advances in understanding membrane protein structure and function.
鉴于整合膜蛋白作为转运体和通道的关键作用，有必要在分子水平上了解它们的结构，因此，了解它们的机制和调节。膜蛋白约占目前测序基因组中所有蛋白质的 30%。然而，矛盾的是，在蛋白质数据库中储存的晶体结构中，只有约 2%是膜蛋白，而且其中很少有达到高分辨率（优于 2A）。我们对可溶性蛋白的理解与我们对膜蛋白的理解之间存在巨大差距，这是因为与膜蛋白相关的实际问题——具体来说，是在表达、纯化和结晶方面的困难。因此，计算建模已被广泛用于在理解膜蛋白结构和功能方面取得重大进展。
