PROTEIN SURFACE DATABASE W/ FAST QUERIES FOR HOMOLOGY

需要通用的工具，以承认简易查询的集合， 蛋白质数据库中的信息已经变得非常重要 不仅在结构生物学领域， 分子生物学家社区，他们对利用结构 阐明序列和结构-功能关系。虽然工具有 被开发来实现数据库查询以找到相似的蛋白质 子结构或类似的三维星座的残留物，迄今没有 已经开发了通用工具来实现基于 蛋白质表面的相似性。这似乎是一个惊人的遗漏：它 是蛋白质表面的形状和性质， 和键特异性，因此负责功能。 一套 用于三维查询、叠加和分析的工具 蛋白质表面会有大量的实际应用 （见下文），并将大大提高 蛋白质数据库中的蛋白质结构集合。是 本提案的目的是发展这种能力，接受查询， 可视化，并分析蛋白质表面的空间和 生化特性工作的起点将包括 用于特征识别的初级地形草图， 在计算机视觉领域的发展，以及收集 生物化学表面分析和可视化工具组装到 哥伦比亚大学开发的流行程序GRASP。 软件和 在这项工作中开发的数据库工具将 商业化。 拟议的商业应用：拟议的表面数据库查询 能力具有潜在的商业用途， 基因产物的功能，在序列的修改， 特异性和功能，在药物分子的设计能够 区分相关蛋白质家族中的靶点， 小分子和肽模拟物的生物化学模拟， 蛋白质表面上的功能表位。

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.