REAL TIME PROTEIN DOMAIN AND FLEXIBILITY IDENTIFICATION

实时蛋白质结构域和灵活性识别

• 批准号: 2715292
• 负责人: Donald JACOBS
• 金额: $ 10万
• 依托单位: MOLFLEX
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2715292
• 关键词: X ray crystallography; computer assisted sequence analysis; computer program /software; computer simulation; computer system design /evaluation; conformation; hydrogen bond; molecular dynamics; physical model; protein engineering; protein sequence; protein structure

Our long-term objective is to develop biotechnology software, based on the FIRST algorithm (Floppy Inclusions and Rigid Substructure Topography) that will offer researchers at pharmaceutical and biotechnology companies a useful set of tools for evaluating protein domains and conformational flexibility for drug design and protein engineering. Developed by an interdisciplinary team, FIRST applies concepts from graph theory to protein structural analysis. The goal of Phase I is to develop and validate FIRST for several proteins with well-characterized conformational states by optimizing the modeling of hydrogen bonds. The rigid and flexible regions identified by FIRST will be compared with traditional measures of flexibility including crystallographic temperature factors and molecular dynamics trajectories. The FIRST algorithm can be used in real time; for example, it can analyze a 200 residue protein and identify flexible hinges and rigid substructures within a fraction of a second using a Pentium PC. The initial product will provide a detailed map for locating rigid motifs and flexible linkages within proteins. This will give the pharmaceutical biochemist the ability to explore, in real time, the effects on ligand structural stability and docking that result from making specific modifications to a protein. PROPOSED COMMERCIAL APPLICATIONS: The commercial applications are to market scientific software for the real-time characterizing of rigid and flexible regions in proteins for crystallographers and pharmaceutical biochemist, as well as an interactive design tool for molecular biologists for evaluating and conformational effects of site-directed mutations.

我们的长期目标是开发基于生物技术的软件 FIRST 算法（软盘夹杂物和刚性子结构拓扑） 这将为制药和生物技术公司的研究人员提供 一套用于评估蛋白质结构域和构象的有用工具 药物设计和蛋白质工程的灵活性。由一个开发 跨学科团队，FIRST 将图论的概念应用于 蛋白质结构分析。第一阶段的目标是开发和 对几种具有良好表征的蛋白质进行 FIRST 验证 通过优化氢键建模来确定构象态。这 FIRST 识别的刚性和柔性区域将与 传统的灵活性测量方法，包括晶体学 温度因素和分子动力学轨迹。第一个 算法可以实时使用；例如，它可以分析 200 残留蛋白质并识别柔性铰链和刚性子结构 使用奔腾 PC 仅需不到一秒的时间。最初的产品 将提供详细的地图，用于定位刚性图案和灵活的图案 蛋白质内部的连接。这将为药物生物化学家提供 实时探索对配体结构的影响的能力 通过进行特定修改而产生的稳定性和对接 一种蛋白质。 拟议的商业应用： 商业应用程序是为了营销科学软件 实时表征蛋白质中的刚性和柔性区域 晶体学家和药物生物化学家，以及 分子生物学家用于评估和评估的交互式设计工具 定点突变的构象效应。