PROTEIN SURFACE DATABASE W/ FAST QUERIES FOR HOMOLOGY

需要通用工具来方便地查询集合 蛋白质数据库中的信息已经成为人们非常感兴趣的 不仅在结构生物学的社区内，而且在 分子生物学家社区对使用结构 阐明序列和结构-功能关系。而工具则有 被开发用于实现数据库查询以查找相似蛋白质 残基的亚结构或类似的3D星座，迄今没有 已经开发了通用工具来实现基于 蛋白质表面之间的相似性。这似乎是一个惊人的遗漏：它 是赋予其锁定的蛋白质表面的形状和性质- AND-键专一性，因此对功能负责。一套 用于三维查询、叠加和分析的工具 蛋白质表面将会有大量的实际应用。 (概述如下)，并将显著提高 蛋白质数据库中蛋白质结构的集合。它是 这项提议的目的是开发这种能力，接受询问， 蛋白质表面的空间和立体结构的可视化和分析 生化特性。这项工作的起点将包括 用于特征识别的初步地形图，具有良好的地形图特征。 在计算机视觉领域开发的，并收集了 生化表面分析和可视化工具组装成 哥伦比亚大学开发了广受欢迎的GRAP程序。软件和 在这项工作中开发的数据库工具将是 商业化了。 拟议的商业应用：拟议的表面数据库查询 功能具有潜在的商业用途 基因产物的功能，在序列的修饰中起决定作用 特异性和功能，在设计药物分子时能够 在相关蛋白质家族中识别靶标，并在设计中 小分子和多肽模拟物的生物化学模拟 蛋白质表面的功能表位。

The need for general tools to admit facile query of the collection of information in the Protein Database has become of significant interest not only within the community of structural biology but also within the community of molecular biologists interested in using structure to elucidate sequence and structure-function relationships. While tools have been developed to implement database queries to find similar protein substructures or similar 3D constellations of residues, to date no general tools have been developed to implement queries based on similarity between protein surfaces. This seems an egregious omission: it is the shape and properties of the protein surface which impart its lock- and-key specificity and are hence responsible for function. A suite of tools for the three dimensional query, superposition, and analysis of protein surfaces would find a plethora of practical applications (outlined below), and would significantly enhance the practical value of the collection of protein structures in the Protein Database. It is the purpose of this proposal to develop such capabilities, admitting queries, visualization, and analyses of protein surfaces in terms of steric and biochemical properties. Starting points for the work will consist of the Primary Topographical Sketch for feature recognition which is well- developed in the field of Computer Vision, and the collection of biochemical surface analysis and visualization tools assembled into the popular program GRASP developed at Columbia University. Software and database tools developed in the course of this work will be commercialized. PROPOSED COMMERCIAL APPLICATION: The proposed surface database query capabilities are of potential commercial use the interpretation of function of gene products, in the modification of sequence to dictate specificity and function, in the design of drug molecules capable of discriminating targets in families of related proteins, and in the design of small-molecule and peptide mimetics which biochemically emulate a functional epitope on a protein surface.