Dell'Orco Daniele
Department of Chemistry, University of Modena and Reggio Emilia, Via Campi 183, 41100, Modena, Italy.
Mol Biosyst. 2009 Apr;5(4):323-34. doi: 10.1039/b821580d. Epub 2009 Feb 19.
The increasing call for an overall picture of the interactions between the components of a biological system that give rise to the observed function is often summarized by the expression systems biology. Both the interpretative and predictive capabilities of holistic models of biochemical systems, however, depend to a large extent on the level of physico-chemical knowledge of the individual molecular interactions making up the network. This review is focused on the structure-based quantitative characterization of protein-protein interactions, ubiquitous in any biochemical pathway. Recently developed, fast and effective computational methods are reviewed, which allow the assessment of kinetic and thermodynamic features of the association-dissociation processes of protein complexes, both in water soluble and membrane environments. The performance and the accuracy of fast and semi-empirical structure-based methods have reached comparable levels with respect to the classical and more elegant molecular simulations. Nevertheless, the broad accessibility and lower computational cost provide the former methods with the advantageous possibility to perform systems-level analyses including extensive in silico mutagenesis screenings and large-scale structural predictions of multiprotein complexes.
对生物系统各组成部分之间相互作用的整体情况的呼声日益高涨，这些相互作用产生了所观察到的功能，这通常用“系统生物学”这一表述来概括。然而，生化系统整体模型的解释和预测能力在很大程度上取决于构成网络的各个分子相互作用的物理化学知识水平。本综述聚焦于蛋白质 - 蛋白质相互作用基于结构的定量表征，这种相互作用在任何生化途径中都普遍存在。文中回顾了最近开发的快速有效的计算方法，这些方法能够评估蛋白质复合物在水溶性和膜环境中的缔合 - 解离过程的动力学和热力学特征。快速且基于半经验结构的方法的性能和准确性已达到与经典且更精确的分子模拟相当的水平。尽管如此，广泛的可及性和较低的计算成本为前一类方法提供了进行系统水平分析的有利可能性，包括广泛的计算机模拟诱变筛选和多蛋白复合物的大规模结构预测。
