REAL TIME PROTEIN DOMAIN AND FLEXIBILITY IDENTIFICATION

我们的长期目标是开发生物技术软件，基于 第一种算法(软包裹体和刚性子结构拓扑学) 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 跨学科团队，首先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 首先验证几种具有良好特性的蛋白质 通过优化氢键模型的构象状态。这个 First确定的刚性和弹性区域将与 包括结晶学在内的灵活性的传统衡量标准 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，它可以分析一个200 残基蛋白质和识别柔性铰链和刚性亚结构 使用奔腾电脑，不到一秒钟的时间。最初的产品 将提供定位刚性图案和柔性图案的详细地图 蛋白质内部的联系。这将使制药生物化学家 能够实时探索对配体结构的影响 稳定性和对接，这是通过对 一种蛋白质。 建议的商业应用： 商业应用程序是为了销售科学软件 蛋白质刚性区域和柔性区域的实时表征 结晶学家和药物生物化学家，以及 分子生物学家的交互式设计工具，用于评估和 定点突变的构象效应。

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.