Rapid Computational Analysis of Biomolecular Properties

生物分子特性的快速计算分析

• 批准号: 9601463
• 负责人: Barry Honig
• 金额: $ 69.89万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9601463&HistoricalAwards=false
• 关键词: Rapid; Computational; Analysis; Biomolecular; Properties

Project Summary The purpose of the research described in this proposal is the development of rapid computational tools for the analysis of the three dimensional structure of biological macromolecules. The goal is to combine graphical techniques designed to highlight functionally important features of macromolecules with numerical and theoretical methods that allow a user to extract meaningful numbers about important physical properties from a three dimensional structure. Capabilities of this type of have been incorporated into the GRASP (Graphical Representation and Analysis of Structural Properties) computer program which was developed in the current funding period. In the past three years GRASP evolved into one of the most widely used analysis tools in Structural Biology. A goal of the current proposal is to continue the development of GRASP by making it more widely accessible and through the incorporation of new functionalities and new quantitative analysis tools. The major application of GRASP has been the calculation and representation of the electrostatic potentials of proteins and nucleic acids on the molecular surface. The potentials are calculated from finite-difference solutions to the Poisson-Boltzmann (PB) equation obtained from essentially the same algorithm used in the DelPhi program which was also developed in this lab. It has become commonplace for the report of a new structure of a protein to include one or more GRASP pictures representing solutions to the PB equation. However Silicon Graphics workstations are required to depict these images, a factor which has to some extent limited their use. In order to make GRASP images more widely available, we plan to convert the graphical routines within GRASP to output graphical descriptions in VRML, the 3D scene description language proposed for the World Wide Web (WWW). We also plan to introduce interfacing tools which will facilitate communication with other programs, will simplify the learning curve for the use of current functionalities and will make it possible to integrate new quantitative analysis tools within GRASP. A second goal of the current proposal is the creation of a database of GRASP images for the entire Protein Data Base (PDB). GRASP molecular surface images of electrostatic potential and curvature will be created for each protein in the PDB will be stored in a database. 2D and 3D GRASP images will be made available for viewing over the WWW. It is anticipated that the wide availability of these images will lead to the development of a new structure-function relationships and, ultimately, to the creation of new surface-based data bases which will make it possible to deduce function and functionally active regions given a three dimensional structure. The final goal of the proposal is the integration of quantitative analysis tools within GRASP. In particular, a user will be able, in real-time, to obtain pKais solvation, conformational and binding free energies for any structure depicted graphically on the screen. The significance of the proposed research to the advancement of knowledge is manifest in the success of GRASP which has demonstrated the impact of interactive quantitative analysis tools on the analysis of macromolecular structure and function relationships. The database of surface properties and the addition of new GRASP functionalities should have comparable impact on the ability to exploit the vast amount of information embodied in the three dimensional structure of proteins and nucleic acids.

项目摘要本提案中描述的研究的目的是开发快速计算工具，用于分析生物大分子的三维结构。 目的是将旨在突出大分子在功能上重要特征的图形技术与数值和理论方法相结合，这些方法使用户可以从三维结构中提取有关重要物理属性的有意义的数字。这种类型的功能已被纳入当前资金期间开发的计算机程序的GRASP（图形表示和分析）。在过去的三年中，Grasp演变成结构生物学中最广泛使用的分析工具之一。当前建议的目的是通过使其更广泛地访问，并通过合并新的功能和新的定量分析工具来继续开发Grasp。 GRASP的主要应用是蛋白质和核酸在分子表面上的静电电位的计算和表示。 电势是从有限差分解决方案计算到从本实验实验室中开发的Delphi程序中使用的基本相同算法获得的泊松式玻璃体方程。对于蛋白质的新结构的报告已成为司空见惯，包括一个或多个代表PB方程解决方案的图片。 但是，需要硅图形工作站来描绘这些图像，这在某种程度上必须限制其使用。 为了使掌握图像更广泛地可用，我们计划将GRASP内的图形例程转换为VRML中的图形描述，这是3D场景描述为万维网（WWW）提出的3D场景描述语言。 我们还计划引入接口工具，以促进与其他程序进行通信，将简化学习当前功能的学习曲线，并将使将新的定量分析工具集成到GRASP之内。 当前建议的第二个目标是为整个蛋白质数据库（PDB）创建GRASP图像数据库。 将为PDB中的每种蛋白质创建静电电位和曲率的抓握分子表面图像，将存储在数据库中。 2D和3D掌握图像将用于www上方查看。可以预料，这些图像的广泛可用性将导致新的结构功能关系的发展，并最终创建新的基于表面的数据库，这将使在三维结构给定三维结构的情况下推断功能和功能活动区域。该提案的最终目标是将定量分析工具的整合到掌握之内。 特别是，用户将能够实时获得PKAIS溶剂化，构象和绑定的自由能，以适用于屏幕上图形描述的任何结构。 拟议的研究对知识发展的重要性体现在Grasp的成功中，这证明了交互式定量分析工具对大分子结构和功能关系分析的影响。 表面特性的数据库和新的抓紧功能应对利用蛋白质和核酸三维结构中大量信息的能力产生可比的影响。