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，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。基因组中大量的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一个有用的第一步，快速全基因组识别推定的蛋白质功能和结构，计算确定生物相关的合作伙伴的问题的研究才刚刚开始。该项目从两个互补的角度来研究预测蛋白质-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，基于信息的方法的发展。该建议的第一部分集中在一个特定的良好表征的结构基序，介导蛋白质-蛋白质相互作用：平行的，2-链卷曲螺旋。其目标是开发新的计算技术，可以预测两个卷曲螺旋蛋白质是否相互作用。第二部分将扩展几个现有的非结构的全基因组和跨基因组的方法，最初设计用于推断蛋白质功能的预测蛋白质相互作用介导的特定蛋白质相互作用域的问题。该项目的教育目标包括：（1）生物信息学课程开发，包括分子生物学研究生的研究生“计算证书”;（2）在入门级和研究生研究研讨会级开发跨学科生物信息学课程;（3）通过互联网传播教学材料。

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.