The Arabidopsis Proteome Folding Project

纽约大学获得一笔拨款，用于开发一个公共数据库，提供有关两种植物基因组中发现的蛋白质的结构和推断功能的信息。模式物种拟南芥和作物植物Oryza sativa。蛋白质在细胞中合成为长聚合物，折叠形成对其功能至关重要的三维形状；了解蛋白质的三维结构对于推断它们的特定功能至关重要。从蛋白质序列预测蛋白质结构的多种最先进的方法，包括折叠识别方法，其中蛋白质序列被映射到已知的折叠上，以及Rosetta de novo结构预测，其中蛋白质在硅中折叠，将应用于这些植物基因组中的所有注释蛋白质。我们还将把这些结构预测与蛋白质（以及折叠蛋白质上的功能位点）如何进化的知识结合起来，通过估计这些基因组中所有蛋白质结构域家族的系统发育，并使用基于密码子的分子进化模型识别这些蛋白家族中正选择的氨基酸位点，这些模型可以映射到预测结构上。这种结构和进化信息的整合将导致有注释的功能信息推断，这将对研究多种植物物种的生物学家非常有用。这些方法对于植物基因组中功能未知的大部分蛋白质的注释特别有用，其中大多数没有任何3D折叠结构的注释（即与另一种已知结构的蛋白质没有可检测到的相似性）。该项目的生物信息学资源也可扩展应用于其他已测序的植物基因组。该项目是纽约大学和美国自然历史博物馆之间的合作成果，将在世界社区网格（一个由IBM组织的40万志愿者组成的松散耦合计算平台）上进行，以一种经济有效的方式避开所需的全基因组结构预测的计算障碍。通过参与世界社区网格（wcgrid.org），该项目还将提供一个论坛，向跨越所有地理、年龄和社会经济类别的数十万网格参与者解释植物基因组学。最后，该项目将与纽约大学斯坦哈特学院的高中教师继续教育计划相结合，该计划将培训教师如何将生物信息学纳入高中科学课程。

New York University is awarded a grant to develop a public database that provides information about the structure and inferred function of proteins found in two plant genomes ? the model species Arabidopsis thaliana and the crop plant Oryza sativa (rice). Proteins are synthesized in the cell as long polymers that fold to form three-dimensional shapes critical for their function; knowledge of the 3D structure of proteins can be crucial for inferring their specific function. Multiple state-of-the-art methods for predicting protein structure from protein sequences, including fold-recognition approaches, where protein sequences are mapped onto known folds, and Rosetta de novo structure prediction, where proteins are folded in silico, will be applied to all annotated proteins in these plant genomes. We will also integrate these structure predictions with knowledge of how proteins (and functional sites on folded proteins) evolve, by estimating the phylogenies of all protein domain families in these genomes and identifying positively-selected amino acid sites in these prorein families using codon-based molecular evolution models that can be mapped onto the predicted structures. This integration of structural and evolutionary information will result in annotated functional information inferences that will be useful to a wide cross-section of biologists working on several plant species. These methods will be especially useful for annotating the large fraction of proteins in plant genomes whose functions are currently unknown, the majority of which do not have any annotation of 3D folded structure (i.e., no detectable similarity to another protein with known structure). The bioinformatics resources for this project can also be extended for application to other sequenced plant genomes. The project is a collaborative effort between New York University and the American Museum of Natural History and will be carried out on the World Community Grid (a loosely coupled computing platform composed of 400,000 volunteers, organized by IBM), sidestepping the computational barrier to the required genome-wide structure prediction in a cost effective way. By participating in the World Community Grid (wcgrid.org), the project will also provide a forum for explaining plant genomics to several hundred thousand Grid participants spanning all geographic, age, and socioeconomic categories. Finally, the project will be coupled to a continuing education program for high school teachers at the NYU Steinhardt School that will train teachers how to incorporate bioinformatics into high school science curricula.