Continued Development of a Software Framework to Maintain and Query Features of Biological Macromolecules

本提案旨在维护和进一步开发一个面向对象的软件框架，以表示和访问蛋白质，DNA， RNA的大分子结构数据。和它们的复合物。在这种情况下，软件框架意味着一组可重用的软件组件，这些组件包含基于大分子结构的信息的存储、直观、有效的检索和处理，从而更好地理解结构-功能关系。一个持续的主要设计目标是以迄今未想到的方式快速组合和应用这些组件的能力。这是一种对快速发展的结构生物学领域具有特殊价值的方法，在这个领域，数据的数量，我们对数据的了解，以及数据引发的新问题，都在以接近指数的速度持续增长。现有的框架，基于PDBlib，一个表示大分子结构的~++类库，已经接口到各种后端存储格式，包括蛋白质数据库（PDB） ASCII文件。面向对象的PDB （OOPDB - PDBlib的持久版本）和派生特征数据库（DFDB）。所有后端存储格式的查询都可以通过MacroMolecular Query Language （MMQL）进行，这是一种特定于领域的非正式查询方法。更有限的OOPDB和DFDB查询以及从这些数据库生成的报告可以通过万维网（WWW）服务器Macromolecular Object Oriented Search Engine （MOOSE）在全球范围内获得。这一建议寻求维持和扩展框架的所有方面。本提案的具体目标如下：通过圣地亚哥超级计算机中心（SDSC）的资源维护和提供现有的和不断发展的框架。这意味着：提供对当前本地和派生数据的访问、数据库维护、软件维护、软件分发以及对用户社区的有限帮助。将框架扩展到：1。通过扩展PDBlib支持更广泛的生物大分子信息。即大分子的功能分类，不存在三维结构的一级序列，核磁共振系综d~ta，以及包括x射线和核磁共振以外来源的实验数据。2. 提供新的查询方法（主要用于比较分析），以便通过扩展到MMQL有效地使用现有数据和新数据。3. 提供将以前查询的结果存储并随后作为专用数据库进行操作的能力。优化框架使用的存储和查询方法。使用该框架继续进行内部研究，探索蛋白质结构中发现的各种结构参数之间的相关性。虽然还远没有证明社区会使用和进一步开发像这里所建议的这样的软件框架，但在硬件成本下降并没有伴随着软件开发成本的显著下降的情况下，其背后的原理似乎是合理的。

This proposal seeks to maintain and further develop an object oriented software framework to represent and access macromolecular structure data of proteins, DNA, RNA. and their complexes. In this context a software framework implies a set of reusable software components that encompass the storage, intuitive, efficient retrieval and processing of macromolecular structure-based information leading to a better understanding of structure-function relationships. A continuing major design goal is the ability to quickly combine and apply these components in hitherto unthought of ways. An approach of particular value to the fast evolving domain of structural biology where the amount of data, our knowledge about that data, and presumably the new questions that data raises, continues to grow at a near exponential rate. The existing framework, based on PDBlib, a ~++ class library for representing a macromolecular structure, already interfaces to a variety of backend storage formats including Protein Data Bank (PDB) ASCII files. Object Oriented PDB (OOPDB - a persistent version of PDBlib) and a Derived Features DataBase (DFDB). Query of all backend storage formats is available through MacroMolecular Query Language (MMQL), a domain specific non-formal query methodology. More limited query of OOPDB and DFDB and reports generated from these databases are available globally through the Macromolecular Object Oriented Search Engine (MOOSE), a World Wide Web (WWW) server. This proposal seeks to maintain and expand all facets of the framework. The specific goals of this proposal are as follows: Maintain and make available through the resources of the San Diego Supercomputer Center (SDSC) the existing and evolving framework. This implies: providing access to current native and derived data, database maintenance, software maintenance, software distribution, and limited assistance to the community of users. Extend the framework to: 1. Support a broader range of information on biological macromolecules through extensions to PDBlib. Namely, functional classification of macromolecules, primary sequence where no 3-D structure exists, NMR ensemble d~ta, and experimental data including that from sources other than X-ray and NMR. 2. Provide new query methods (predominantly for comparative analysis) to effectively use existing and new data by extensions to MMQL. 3. Provide the ability to store and subsequently operate on the results of previous queries as specialized databases. Optimize the storage and query methodology used by the framework. Continue in-house research using the framework to explore correlations between various structural parameters found in protein structures. While it is far from proven that the community will use and further develop software frameworks such as the one proposed here, the rationale behind it would seem sound in a time when the falling cost of hardware has not been matched by a significantly decreased cost in software development.