Rapid Computational Analysis of Biomolecular Properties

生物分子特性的快速计算分析

• 批准号: 9904841
• 负责人: Barry Honig
• 金额: $ 155.15万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-10-01 至 2005-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9904841&HistoricalAwards=false
• 关键词: Rapid; Computational; Analysis; Biomolecular; Properties

PROJECT SUMMARYThe major objective of the proposed research is the development of computational tools for the analysis of intermolecular interactions involving biological macromolecules. Since such interactions are primarily localized at the molecular surface, particular emphasis will be placed on databases, software, and algorithms for the mapping, analysis and comparison of physical and chemical properties on the molecular surface. The proposed research builds on concepts embodied in the GRASP (Graphical Representation and Analysis of Structural Properties) program which was developed in previous funding periods. The widespread use of GRASP has led to the need for its continued development and integration with the growing body of sequence, structural and functional data currently becoming available, particularly from genome sequencing projects. In parallel, the increasing number of three dimensional protein structures that have been determined, as well as progress in structure prediction has produced both a need and an opportunity for the development of new approaches aimed at extracting functional information from structure.The specific goals of the proposed research include: 1) The development of a new version of GRASP with greater generality and portability and enhanced capabilities to calculate molecular properties such as electrostatic potentials, binding five energies and pKas. The program will be based on a new, multi-platform, object-oriented software library with convenient programmer and user interfaces so as to allow maximum flexibility, extendibility and usability. 2) The use of this program to construct and interrogate a fundamentally new type of database that will contain geometric, physical, chemical and biological descriptions of protein surfaces and interfaces formed by proteins.The proposed research will have significant impact on the understanding of the principles of molecular recognition involving biological macromolecules. The tools to be developed will be used by structural biologists, molecular biologists and biochemists interested in integrating structural information and biophysical methods into their research programs. In addition, this proposal represents an effort to integrate genomic information, structural information, physical chemical principles, mathematical algorithms and software development into a unified research program. The interdisciplinary research and training involved should add to both the scientific and human resource infrastructure of the emerging area of Structural Genomics.

项目总结所提出的研究的主要目的是开发用于分析涉及生物大分子的分子间相互作用的计算工具。由于这种相互作用主要位于分子表面，因此将特别重点放在数据库，软件和算法上，以绘制，分析和比较分子表面上的物理和化学特性。拟议的研究基于在以前的资助期间开发的GRASP（图形表示和结构属性分析）计划中所体现的概念。 GRASP的广泛使用已导致其与序列，结构和功能数据的不断发展，尤其是基因组测序项目的持续发展和整合。同时，已经确定的三维蛋白质结构的增加数量以及结构预测的进步既产生了需求，又产生了开发旨在从结构中提取功能信息的新方法的机会。拟议的研究的具体目标包括：1）开发具有更大的一般性和携带能力的新版本，可以增强能力和能力，以计算出五个能力，例如构成分子的能力。该程序将基于具有方便的程序员和用户界面的新的，多平台的，面向对象的软件库，以允许最大程度的灵活性，可扩展性和可用性。 2）使用该程序来构建和询问一种从根本上进行的新型数据库，该数据库包含对蛋白质表面和蛋白质形成的蛋白质表面的几何，化学和生物学描述。拟议的研究将对涉及生物学大分子的分子识别原理产生重大影响。结构性生物学家，分子生物学家和生物化学家将使用这些工具使用，该工具有兴趣将结构信息和生物物理方法整合到其研究计划中。 此外，该提案代表了将基因组信息，结构信息，物理化学原理，数学算法和软件开发整合到统一研究计划中的努力。涉及的跨学科研究和培训应增加结构基因组学新兴领域的科学和人力资源基础设施。