PECASE: Computational Methods for Genome-Wide Prediction of Protein-Protein Interactions

这项研究的长期目标是开发在基因组水平上预测蛋白质-蛋白质相互作用的计算方法。蛋白质-蛋白质相互作用在生物体的功能中起着核心作用，而预测这些相互作用的计算方法将是理解生物系统内功能途径的关键。基因组中的海量生物序列数据使得复杂的计算分析成为必要。虽然计算方法已经被证明是在全基因组范围内快速鉴定假定的蛋白质功能和结构的有用的第一步，但关于通过计算确定给定蛋白质序列的生物相关伙伴的问题的研究才刚刚开始。这个项目从两个互补的角度着眼于预测蛋白质-蛋白质相互作用的问题。对于这两种方法，基因组水平分析的限制有利于快速、基于信息学的方法的发展。这项提议的第一部分集中在一个特定的、特征良好的结构基序上，它介导蛋白质-蛋白质相互作用：平行的、双股螺旋线圈。其目标是开发新的计算技术，可以预测两个卷曲卷曲蛋白质是否相互作用。第二部分将把最初设计用于推断蛋白质功能的几种现有的非结构、全基因组和跨基因组方法扩展到预测由特定蛋白质相互作用结构域介导的蛋白质-蛋白质相互作用的问题。该项目的教育目标包括：(1)开发生物信息学课程，包括为分子生物学研究生颁发研究生“计算证书”；(2)在入门一级和研究生研究研讨会一级开发跨学科生物信息学课程；(3)通过因特网传播教学材料。

The long-term goal of this research is to develop computational methods for predicting protein-protein interactions at a genomic level. Protein-protein interactions play a central role in how an organism functions, and computational methods for predicting these interactions will be key to understanding functional pathways within biological systems. The vast amount of biosequence data in a genome makes sophisticated computational analysis a necessity. While computational methods have already proven to be a useful first step for rapid genome-wide identification of putative protein function and structure, research on the problem of computationally determining biologically relevant partners for given protein sequences is just beginning. This project looks at the problem of predicting protein-protein interactions from two complementary viewpoints. For both approaches, the constraint of genomic-level analysis favors development of fast, informatics-based methods. The first part of this proposal focuses on a specific well-characterized structural motif that mediates protein-protein interactions: the parallel, 2-stranded coiled coil. The goal is to develop novel computational techniques that can predict whether two coiled-coil proteins interact with each other. The second part will extend several existing non-structural whole- and cross-genome methodologies that were initially designed for inferring protein function to the problem of predicting protein-protein interactions mediated by particular protein interaction domains. The educational goals of this project include: (1) bioinformatics curriculum development, including a graduate "computing certificate" for molecular biology graduate students; (2) development of interdisciplinary bioinformatics courses at the introductory level and at the graduate research seminar level; and (3) dissemination of instructional material via the internet.