Department of Medical Protein Research, VIB, Ghent, Belgium.
Curr Pharm Des. 2012;18(30):4619-29. doi: 10.2174/138161212802651562.
Physical interactions among proteins constitute the backbone of cellular function, making them an attractive source of therapeutic targets. Although the challenges associated with targeting protein-protein interactions (PPIs) -in particular with small molecules - are considerable, a growing number of functional PPI modulators is being reported and clinically evaluated. An essential starting point for PPI inhibitor screening or design projects is the generation of a detailed map of the human interactome and the interactions between human and pathogen proteins. Different routes to produce these biological networks are being combined, including literature curation and computational methods. Experimental approaches to map PPIs mainly rely on the yeast two-hybrid (Y2H) technology, which have recently shown to produce reliable protein networks. However, other genetic and biochemical methods will be essential to increase both coverage and resolution of current protein networks in order to increase their utility towards the identification of novel disease-related proteins and PPIs, and their potential use as therapeutic targets.
蛋白质之间的物理相互作用构成了细胞功能的基础，使它们成为治疗靶点的有吸引力的来源。尽管靶向蛋白质-蛋白质相互作用 (PPI) 的挑战——特别是对于小分子来说——相当大，但越来越多的功能性 PPI 调节剂正在被报道和临床评估。PPI 抑制剂筛选或设计项目的一个基本起点是生成人类相互作用组和人类与病原体蛋白之间相互作用的详细图谱。正在结合不同的方法来产生这些生物网络，包括文献整理和计算方法。绘制 PPI 的实验方法主要依赖于酵母双杂交 (Y2H) 技术，该技术最近已被证明可产生可靠的蛋白质网络。然而，其他遗传和生化方法对于增加当前蛋白质网络的覆盖范围和分辨率至关重要，以便提高它们在识别新型疾病相关蛋白和 PPI 及其作为治疗靶点的潜在用途方面的效用。
