Protein Functional Site Characterization and Analysis

描述（由申请人提供）：本提案的广泛目标是建立一个计算平台，通过整合来自结构基因组学、功能基因组学和化学基因组学的数据，并使用来自生物信息学、化学信息学和生物物理学的工具，在从分子到细胞的多尺度上预测和理解蛋白质功能。在蛋白质组学时代，蛋白质很容易分离，但不容易以任何程度的信心进行功能分类，因此迫切需要满足这一目标。作为第一步，我们在这里提出：（1）设计和实现可扩展的，准确的，可靠的和鲁棒的算法和相关软件，用于预测，比较，搜索和分类蛋白质功能位点和蛋白质配体相互作用;（2）设计并实现了一个本体驱动的蛋白质功能位点及蛋白质-配体相互作用数据库，和突变信息，并支持在基因组规模上对蛋白质结构和功能进行定量建模;（3）首先建立一个直观的图形用户界面（GUI），供科学家可视化，分析和挖掘比较蛋白质组学的功能位点信息，然后建立应用程序编程接口（API），为程序员开发新的算法和应用程序使用这里提出的基础。这项工作的结果将通过蛋白质数据库传播，每天有10 000多名科学家使用该数据库。

DESCRIPTION (provided by applicant): The broad objective of this proposal is to establish a computational platform to predict and understand protein functions at multi-scales, from molecule to cell, through integrating data from structural genomics, functional genomics and chemical genomics, and using tools derived from bioinformatics, chemical informatics and biophysics. There is a serious need to meet this objective in an era of proteomics where proteins are easily isolated, yet not so easily functionally classified with any degree of confidence. As the first step we propose here to: (1) design and implement scalable, accurate, reliable and robust algorithms and associated software for predicting, comparing, searching, and classifying protein functional sites and proteinligand interactions; (2) design and implement an ontology-driven protein functional site and protein-ligand interaction database that integrates comprehensive structure, function, and mutation information and supports quantitative modeling of protein structure and functions at the genome scale; (3) Establish first an intuitive graphical user interfaces (GUI) for scientists to visualize, analyze and mine functional site information for comparative proteomics and second establish an application programming interface (API) for programmers to develop new algorithms and applications using the foundation proposed here. The results of this effort will be disseminated through the Protein Data Bank which is used by over 10,000 scientists every day.