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.

本课题的研究目的是开发用于分析生物大分子三维结构的快速计算工具。目标是将图形技术与数值和理论方法相结合，以突出大分子的重要功能特征，使用户能够从三维结构中提取有关重要物理性质的有意义的数字。这种类型的能力已经被纳入了GRASP（结构特性图形表示和分析）计算机程序中，该程序是在当前资助期间开发的。在过去的三年中，GRASP已发展成为结构生物学中应用最广泛的分析工具之一。当前提案的一个目标是通过整合新功能和新的定量分析工具，使其更广泛地可访问，从而继续发展GRASP。GRASP的主要应用是计算和表示蛋白质和核酸在分子表面的静电电位。电位由泊松-玻尔兹曼（PB）方程的有限差分解计算得到，其算法与本实验室开发的DelPhi程序基本相同。一个蛋白质的新结构的报告中包含一个或多个表示PB方程解的GRASP图片已经成为司空见惯的事情。然而，硅图形工作站需要描绘这些图像，这在某种程度上限制了它们的使用。为了使GRASP图像更广泛地可用，我们计划将GRASP中的图形例程转换为用VRML输出图形描述，VRML是为万维网（WWW）提出的3D场景描述语言。我们还计划引入接口工具，以促进与其他程序的通信，简化使用当前功能的学习曲线，并使新的定量分析工具集成到GRASP中成为可能。当前提案的第二个目标是为整个蛋白质数据库（PDB）创建一个GRASP图像数据库。GRASP分子表面的静电势和曲率图像将被创建，PDB中的每个蛋白质将被存储在数据库中。2D和3D的GRASP图像将可以在WWW上观看。预计这些图像的广泛可用性将导致新的结构-功能关系的发展，并最终导致新的基于表面的数据库的创建，这将有可能推断出给定三维结构的功能和功能活跃区域。提案的最终目标是在GRASP中集成定量分析工具。特别是，用户将能够实时获得pKais的溶剂化、构象和结合自由能，用于屏幕上图形化的任何结构。我们所提出的研究对知识进步的意义体现在GRASP的成功上，它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。表面特性数据库和新的GRASP功能的添加应该对利用蛋白质和核酸三维结构中包含的大量信息的能力产生类似的影响。