Synthetic Mimetics of Alpha-helix Structure and Function

α-螺旋结构和功能的合成模拟物

• 批准号: 6997800
• 负责人: ANDREW D HAMILTON
• 金额: $ 27.35万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6997800
• 关键词: biomimetics; biotechnology; biphenyl compounds; guanine nucleotide exchange factors; intermolecular interaction; peptide structure; protein binding; protein engineering; protein protein interaction; protein structure function; pyrimidines; synthetic peptide; transcription factor

The convergence of digital design models, networking technologies and computational approaches to the display and manipulation of scientific data makes possible the development of new ways of managing and displaying information. In the biological sciences, these developments have given rise to the field of bioinformatics, where significant advances have been made in areas such as the human genome project and analysis of microarray data. Within the neurosciences, progress has been hampered, in part, by the parochial nature of the data, the lack of consensus on what type of information is most relevant to specific scientific goals, and limited application of design principals to insure effective, intuitive and truly interactive display of information. Most informatics tools under development are focused on the management of primary data. However, it is clear that second-order tools, such as the one proposed here, will be equally important in providing a visual display of the status of proposed hypotheses, and the data supporting them, in specific areas of neuroscience and in other data-rich fields. The goal is to develop a web-based, dynamic information model (DISPLAY) for visualizing and manipulating causal mechanisms proposed to be involved in Alzheimer's disease. The DISPLAY and its dynamic graphic interface will reveal patterns, pathways and conceptual connections not readily apparent from individual research studies. The expertise brought together for this project includes an investigator actively studying Alzheimer's disease, a graphical designer with extensive experience in design principles and the visual display of information, a computer scientist with experience in database management and an expert team in bioinformatics. Phase I will involve development of a working model that depicts the major hypotheses proposed to account for Alzheimer's disease and will be displayed through a web-based Flash interface. Datamining will be initially accomplished through recruitment of curators working in the field who will enter key information into a large biological object model database currently being developed within the Children's Hospital Medical Center Informatics Program. Testing of the model will be carried out by making the model available to investigators through the Alzheimer Research Forum, a widely used web site for Alzheimer's disease research. The model will be built from expert annotator input, automated data capture methods, and will interface with primary literature (available through PubMed). User interfaces and application development will incorporate state-of-the-art design principles. Although the prototype will be based on specific literature mined from the Alzheimer's disease field, the structure of the model will be developed with the goal of being adaptable to other areas of investigation within the neurosciences and, eventually, other areas of science.

数字设计模型、网络技术和计算方法在科学数据显示和处理方面的融合，使得开发管理和显示信息的新方法成为可能。在生物科学中，这些发展带来了生物信息学领域，在人类基因组计划和微阵列数据分析等领域取得了重大进展。在神经科学中，进展受到阻碍，部分原因是数据的狭隘性，在什么类型的信息与特定的科学研究最相关的问题上缺乏共识。 目标和有限的应用程序的设计原则，以确保有效，直观和真正的交互式显示信息。大多数正在开发的信息学工具都侧重于原始数据的管理。然而，很明显，在神经科学的特定领域和其他数据丰富的领域，像这里提出的这样的二阶工具在提供所提出假设的状态以及支持它们的数据的可视化显示方面同样重要。我们的目标是开发一个基于网络的动态信息模型（DynamicInformationModel，简称DMC），用于可视化和操纵阿尔茨海默病的因果机制。该系统及其动态图形界面将揭示模式、路径和 概念上的联系在个别研究中并不明显。为该项目汇集的专门知识包括一名积极研究阿尔茨海默病的调查员、一名在设计原则和信息视觉显示方面具有丰富经验的图形设计师、一名具有数据库管理经验的计算机科学家和一个生物信息学专家小组。第一阶段将涉及开发一个工作模型，描述为解释阿尔茨海默病而提出的主要假设，并将通过基于网络的Flash界面显示。数据挖掘最初将通过招聘在该领域工作的策展人来完成，他们将把关键信息输入到大型生物对象中 模型数据库目前正在儿童医院医疗中心信息学计划内开发。该模型的测试将通过阿尔茨海默病研究论坛（一个广泛使用的阿尔茨海默病研究网站）向研究人员提供模型来进行。该模型将根据专家注释者输入、自动化数据采集方法构建，并将与主要文献（可通过PubMed获得）对接。用户界面和应用程序开发将采用最先进的设计原则。虽然原型将基于从阿尔茨海默病领域挖掘的特定文献，但模型的结构将以适应神经科学内的其他研究领域并最终适应其他科学领域的目标进行开发。