REAL TIME PROTEIN DOMAIN AND FLEXIBILITY IDENTIFICATION

我们的长期目标是开发生物技术软件， FIRST算法（Floppy Inclusions and Rigid Substructure Topography） 为制药和生物技术公司的研究人员提供 一套有用的工具，用于评估蛋白质结构域和构象 药物设计和蛋白质工程的灵活性。由一个 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 验证FIRST用于几种具有良好特征的蛋白质 通过优化氢键的建模来优化构象状态。的 FIRST确定的刚性和柔性区域将与 传统的柔性测量方法， 温度因素和分子动力学轨迹。第一 算法可以用于真实的时间;例如，它可以分析200 残基蛋白质和确定柔性铰链和刚性亚结构 在几分之一秒之内使用奔腾PC。初始产品 将提供一个详细的地图定位刚性图案和灵活的 蛋白质内的连接。这将给制药生物化学家 能够在真实的时间内探索配体结构的影响， 稳定性和对接的结果作出具体的修改， 蛋白质。 拟议的商业应用： 商业应用是为市场销售科学软件， 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 分子生物学家的交互式设计工具， 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.