Nonparametric Bayesian Approaches to Modeling Protein Structure

描述（由申请人提供）：该提案的目标是开发一类新的统计模型，以推进蛋白质三级结构的科学知识，并将基于模板的建模扩展到蛋白质环区域。随着基础科学的进步，蛋白质结构建模的改进将对生物医学领域产生广泛的影响。将实现以下具体目标。第一个目标（按成对信息索引的随机分区模型）是为显式不可交换的分区开发概率模型，利用可用的成对信息来影响数据的聚类。提出了四种分布，每种分布都使用成对信息，通过修改中国餐馆过程中的身份，一个流行的概率模型聚类。层次聚类使用成对距离，但目前的蛋白质结构建模方法没有。所提出的方法提供了一种手段，将这种类型的信息到贝叶斯非参数模型的蛋白质结构。第二个目标（基于模板的建模环构象空间使用分区模型）应用所提出的随机分区模型在环建模。这个建议将改善我们以前的估计方法，占个别氨基酸的影响，以及从相邻残基的影响。基于随机分配模型的新方法将在残基位置处和残基位置之间提供严格的统计建模，从而允许限制构象空间并对其进行精确采样。这反过来又可以更清楚地了解环在催化位点和蛋白质信号传导中的作用。最终目标（使用分区模型的蛋白质包装和高阶结构的新范式）应用统计建模来估计称为“球/窝”的蛋白质包装的新模型的倾向。“球/窝”基序内和基序模式之间的氨基酸倾向的统计建模将允许洞察管理包装的规则，填补了目前对蛋白质结构理解的重大空白。估计这些倾向的统计模型将利用已知的成对信息，通过使用所提出的随机分区模型。科学界目前还没有这种分析。

DESCRIPTION (provided by applicant): This proposal's objective is to develop a new class of statistical models to advance scientific knowledge of protein tertiary structure and to extend template-based modeling to protein loop regions. As advancement in basic science, the improved modeling of protein structure will broadly impact biomedical fields. The following specific aims will be accomplished. The first aim (Random Partition Models Indexed by Pairwise Information) is to develop probability models for partitions that are explicitly non-exchangeable, utilizing available pairwise information to influence the clustering of data. Four distributions ar proposed, each using the pairwise information by modifying identities from the Chinese Restaurant Process, a popular probability model for clustering. Hierarchical clustering uses pairwise distance, but current methods for protein structure modeling do not. The proposed method provides a means to incorporate this type of information into Bayesian nonparametric models for protein structure. The second aim (Template-Based Modeling of Loop Conformation Space Using Partition Models) applies the proposed random partition models in loop modeling. This proposal will improve our previous estimation approach by accounting for the influences of individual amino acids as well as for influences from neighboring residues. New methods based on the random partition models will provide rigorous statistical modeling at and between residue positions allowing one to limit and precisely sample the conformational space. This will in turn allow for a clearer understanding of roles of loops in catalytic sites and protein signaling. The final aim (New Paradigm for Protein Packing and Higher-Order Structure Using Partition Models) applies the statistical modeling to estimate the propensities of a new model of protein packing called the "ball/socket." Statistical modeling of the amino acid propensities within the "ball/socket" motifs and between patterns of motifs will allow insights into the rules governing packing, filling a substantial gap in current understanding of protein structure. The statistical model estimating these propensities will exploit the known pairwise information by using the proposed random partition models. Such analysis is currently not available to the scientific community.