EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG) and UPF, Barcelona, Spain.
Curr Opin Struct Biol. 2011 Aug;21(4):452-9. doi: 10.1016/j.sbi.2011.05.002. Epub 2011 Jun 16.
Structure-based computational methods are popular tools for designing proteins and interactions between proteins because they provide the necessary insight and details required for rational engineering. Here, we first argue that large-scale databases of fragments contain a discrete but complete set of building blocks that can be used to design structures. We show that these structural alphabets can be saturated to provide conformational ensembles that sample the native structure space around energetic minima. Second, we show that catalogs of interaction patterns hold the key to overcome the lack of scaffolds when computationally designing protein interactions. Finally, we illustrate the power of database-driven computational protein design methods by recent successful applications and discuss what challenges remain to push this field forward.
基于结构的计算方法是设计蛋白质和蛋白质相互作用的流行工具，因为它们为合理的工程设计提供了必要的洞察力和细节。在这里，我们首先认为，碎片的大规模数据库包含离散但完整的构建块集，可用于设计结构。我们表明，这些结构字母表可以被饱和，以提供构象集合，这些集合可以在能量极小值周围的天然结构空间中进行采样。其次，我们表明，交互模式目录是克服计算设计蛋白质相互作用时缺乏支架的关键。最后，我们通过最近的成功应用说明了基于数据库的计算蛋白质设计方法的强大功能，并讨论了推动该领域发展的剩余挑战。
