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.

我们的长期目标是基于 第一种算法（软盘包含和僵化的子结构地形） 这将为药品和生物技术公司的研究人员提供 一组有用的工具，用于评估蛋白质域和构象 药物设计和蛋白质工程的灵活性。由An开发 跨学科团队，首先应用了从图理论到 蛋白质结构分析。第一阶段的目的是发展和 首先验证几种具有良好特征的蛋白质 通过优化氢键的建模来构象状态。这 首先确定的刚性和灵活区域将与 传统的灵活性措施，包括晶体学 温度因子和分子动力学轨迹。第一个 算法可以实时使用；例如，它可以分析200 残留蛋白并识别柔性铰链和刚性子结构 在一秒钟内使用奔腾PC。初始产品 将提供一个详细的地图，用于定位刚性图案和灵活 蛋白质中的连锁。这将提供药物生物化学家 实时探索配体结构的影响的能力 稳定性和对接是由于对 蛋白质。 拟议的商业应用： 商业应用是为了推销科学软件 实时表征蛋白质中刚性和柔性区域的特征 晶体学家和药物生化家，以及 分子生物学家的交互式设计工具，用于评估和 位置导向突变的构象作用。