Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
PLoS One. 2012;7(2):e31437. doi: 10.1371/journal.pone.0031437. Epub 2012 Feb 8.
Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs that represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures.
大多数生物过程都被描述为一系列蛋白质和其他分子之间的相互作用，而这些相互作用又可以用原子结构来描述。为了在原子分辨率下将蛋白质功能注释为一系列相互作用状态，从而更好地理解蛋白质相互作用与生物功能之间的关系，我们对所有已知的配体（包括小分子、蛋白质和核酸）的结合位点进行了详尽的全对全原子结构比较，并确定了反复出现的基本基序。通过整合与每个亚基相关的基本基序，我们定义了复合基序，这些基序代表了基本基序的上下文相关组合。结果表明，与蛋白质序列或单个结合位点的相似性相比，从复合基序的相似性可以更好地推断功能相似性。通过整合与每个蛋白质功能相关的复合基序，我们定义了元复合基序，每个元复合基序都被视为生物过程的时间独立图式表示。结果表明，元复合基序比序列聚类提供了更丰富的生物过程注释。这些结果为通过分类和整合结合位点结构将原子结构与更高阶的生物现象联系起来奠定了基础。
