PNAS：蛋白质互作模型或可以提供新的癌症疗法

近日，来自堪萨斯大学的研究者llya Vakser表示，蛋白质并不是多刚体（rigid bodies），它们可以改变形状并且非常灵活，因此我们常常可以将两个完全不匹配的蛋白质进行互相匹配。数年来，科学家依赖于计算机模型技术来表征蛋白质的特征，当然这种精确的计算机模型技术是基于通过X射线晶体学和核磁共振技术来对蛋白质的结构进行模板定位的。

直到现在，这种模板的实际应用价值对于蛋白-蛋白复合物是可用的。研究者发现了几乎完整的设置模型已经存在，这对于结构生物学来说意义深远，这意味未来某些疾病的新药研发提供一些线索。相关研究成果刊登在了国际著名杂志PNAS上。

对蛋白质互作很好的把握对于开发新药和通过改变蛋白质的行为而有利于人类健康治疗手段异常关键。研究者表示，你可以想象一下，蛋白质世界作用一个拥挤复杂的环境，在这种环境中，单一分子可以任意浮游着，而且可以进行互相碰撞；如果只是随机反应的话，并不会发生什么。但是如果单一分子有着生理学的重要性，他们就可能会互相依附，并且改变形状或者转移电子。

影响蛋白质之间互作的能力意味着新的疗法来治疗癌症和冠心病。这将给与我们足够的能力去模拟这些蛋白质的反应并且发现治疗疾病的路径。许多疾病都是由于蛋白质反应的异常情况所引起的，或者这种反应不被希望。但是通过药物来进行调节，我们需要知道其具体的作用原理和机制。本研究中，研究者提出了新的方法来影响蛋白质之间的相互作用，并且研究者后期会立即设计新的治疗手段来治疗某些疾病。

编译自：Research discovery: Near-complete set of templates for protein complexes exists today

编译者：T.Shen

doi:10.1073/pnas.1200678109
PMC:
PMID:

Templates are available to model nearly all complexes of structurally characterized proteins

Petras J. Kundrotasa, Zhengwei Zhub, Joël Janinc,1, and Ilya A. Vaksera,1

Traditional approaches to protein–protein docking sample the binding modes with no regard to similar experimentally determined structures (templates) of protein–protein complexes. Emerging template-based docking approaches utilize such similar complexes to determine the docking predictions. The docking problem assumes the knowledge of the participating proteins’ structures. Thus, it provides the possibility of aligning the structures of the proteins and the template complexes. The progress in the development of template-based docking and the vast experience in template-based modeling of individual proteins show that, generally, such approaches are more reliable than the free modeling. The key aspect of this modeling paradigm is the availability of the templates. The current common perception is that due to the difficulties in experimental structure determination of protein–protein complexes, the pool of docking templates is insignificant, and thus a broad application of template-based docking is possible only at some future time. The results of our large scale, systematic study show that, surprisingly, in spite of the limited number of protein–protein complexes in the Protein Data Bank, docking templates can be found for complexes representing almost all the known protein–protein interactions, provided the components themselves have a known structure or can be homology-built. About one-third of the templates are of good quality when they are compared to experimental structures in test sets extracted from the Protein Data Bank and would be useful starting points in modeling the complexes. This finding dramatically expands our ability to model protein interactions, and has far-reaching implications for the protein docking field in general.