Evolutionary Analysis of Proteins using HyperChem

描述(由申请人提供)： 当蛋白质序列在功能限制下以不同的方式进化时，蛋白质序列会显示出各种“高阶”现象。这些包括序列中不同位置的相关替换，不同位置和进化树不同部分的突变模式的变化，以及收敛和并行的序列进化。这些现象携带着具有生物医学和科学意义的信息，包括关于蛋白质折叠、蛋白质行为、蛋白质-蛋白质相互作用和蛋白质功能的信息。那些寻求解释全球蛋白质组的人会发现一个有价值的工具，它允许在蛋白质三维结构的背景下可视化这些进化现象。这项提案寻求资金，以建立科学调查基金会和HyperCube之间的技术转移合作。科学调查基金会是一个非营利性组织，作为其研究和教育任务的一部分，它开发解释性蛋白质组学策略；HyperCube是一家营利性公司，负责分发HyperChem，这是一个使用量子力学、分子建模和图形可视化分析化学结构的计算机软件包。这一合作的产品将是HyperChem的增强版本，它将显示有趣的高阶现象的残基放在蛋白质家族“共识折叠”的三维模型上，然后在图形用户界面中显示该模型，供用户分析。这种伙伴关系的优势是，基金会已经开发了许多科学概念，并在案例研究中对这些概念进行了验证，而HyperChem已经包含了许多实现可视化的基本程序模块。这一合作关系还将利用HyperChem在全美化学、生物化学和分子生物学部门的广泛市场。基金会已经与EraGen生物科学公司合作开发的产品并不能有效地进入这个教育市场。然而，这也将是HyperChem的一个新方向，并为包括制药和生物技术公司在内的非教育性客户打开HyperCube产品的市场。

DESCRIPTION (provided by applicant): Various "higher order" phenomena are displayed by protein sequences as they divergently evolve under functional constraints. These include correlated replacement at different sites in the sequence, changing patterns of mutation at different sites and in different parts of the evolutionary tree, and convergent and parallel sequence evolution. These phenomena carry information that has biomedical and scientific significance, including information about protein folding, protein behavior, protein-protein interactions, and protein function. Those seeking to interpret the global proteome would find valuable a tool that permits the visualization of these evolutionary phenomena within the context of a three dimensional structure of the protein. This proposal seeks funding to establish a technology transfer collaboration between the Foundation for Scientific Inquiry, a nonprofit organization that develops interpretive proteomics strategies as part of its research and education missions, and HyperCube, a for-profit concern that distributes HyperChem, a computer software package that analyzes chemical structures using quantum mechanics, molecular modeling, and graphics visualization. The product of this collaboration will be an enhanced version of HyperChem that places residues displaying interesting higher order phenomena on to a three dimensional model of the "consensus fold" of the protein family, and then displays this model in a graphic user interface for a user to analyze. The advantage of this partnership is that the Foundation already has developed many of the scientific concepts, and validated these in case studies, while HyperChem already incorporates many of the basic program modules that enable visualization. The partnership will also take advantage of HyperChem's wide market within chemistry, biochemistry, and molecular biology departments across the United States. This educational market is not reached effectively by the product that the Foundation has already developed with EraGen Biosciences. This will also, however, be a new direction for HyperChem, and open a market for HyperCube's product for non-educational customers, including pharmaceutical and biotechnology companies.