Shim Jung Eun, Lee Insuk
Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
Methods Mol Biol. 2020;2074:35-44. doi: 10.1007/978-1-4939-9873-9_3.
Proteins are major functional molecules that physically and functionally interact to carry out cellular processes. The physical interactions are generally mediated by domain-level interactions. Thus, novel protein-protein interactions can be predicted using various computational methods based on domain-domain interactions, using resolved structures of protein complexes. Functional protein interactions can be inferred based on shared domains between proteins, since proteins involved in the same biological processes tend to harbor common domains. We recently developed a method of inferring functional interactions between proteins using associations between their domain compositions, which can be represented as domain profiles. Since the method requires only protein domain annotations, it can be easily applied to any species with a sequenced genome. Here, we describe in detail the method of generating domain profiles for proteins and measuring the association between them to infer functional interactions between proteins. We also demonstrate that domain profile association can be used to successfully construct a large-scale functional network of human proteins.
蛋白质是主要的功能分子，它们在物理和功能上相互作用以执行细胞过程。物理相互作用通常由结构域水平的相互作用介导。因此，可以使用基于结构域-结构域相互作用的各种计算方法，利用蛋白质复合物的解析结构来预测新的蛋白质-蛋白质相互作用。功能性蛋白质相互作用可以基于蛋白质之间共享的结构域来推断，因为参与相同生物学过程的蛋白质往往具有共同的结构域。我们最近开发了一种利用蛋白质结构域组成之间的关联来推断蛋白质之间功能相互作用的方法，这种关联可以表示为结构域谱。由于该方法只需要蛋白质结构域注释，因此可以很容易地应用于任何具有测序基因组的物种。在这里，我们详细描述了为蛋白质生成结构域谱并测量它们之间的关联以推断蛋白质之间功能相互作用的方法。我们还证明了结构域谱关联可用于成功构建大规模的人类蛋白质功能网络。
