Collaborative Research: A General Approach to the Design of Tailor-Made Glycan Recognition Protein Modules.

合作研究：设计定制聚糖识别蛋白模块的通用方法。

• 批准号: 1121276
• 负责人: Giovanna Ghirlanda
• 金额: $ 60.73万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1121276&HistoricalAwards=false
• 关键词: Collaborative; Research; General; Approach; Design

Protein-carbohydrate interactions play an important role in several biological processes, such as cell growth and differentiation, signal transduction, apoptosis, and fertilization. From a molecular recognition perspective, glycans are challenging ligands, in that they differ from each other simply by the point of attachment to each other, or by the position of single hydroxyl groups. Further, glycan based biopolymers are flexible and highly hydrated. The objective of this project is to understand at the molecular level protein-glycan interactions in a model system, and to use this knowledge to develop novel glycan recognition proteins through an integrated computational and experimental strategy. Starting from a natural glycan binding protein, cyanovirin, we will explore the sequence space that supports high-affinity binding to the target glycan in parallel, utilizing directed evolution on the experimental side, and fast docking methods as well as explicit solvent molecular dynamics simulations on the computational side.The Broader Impact of this proposal is twofold. First, the project relies on a highly interdisciplinary approach, which offers students at the graduate and undergraduate level a rich training experience. Second, the PIs participate in outreach activities at the high school level both at Iowa and at ASU. At ASU, Ozkan and Ghirlanda participate with this project to the ASU Math and Science Teaching Fellows program run by CRESMET (http://cresmet.asu.edu/MSTF/index.shtml). The program brings high school teachers from disadvantaged schools in the Phoenix area to ASU for research internships combined with intensive training in science education techniques, and establishes a rapport between schools and university that continues through campus visits. Margulis has created a mentor matching program (http://mentor.chem.uiowa.edu/) that through the Upward Bound Program integrates underrepresented high school students in research groups.

蛋白质-碳水化合物相互作用在细胞生长和分化、信号转导、细胞凋亡和受精等生物过程中发挥着重要作用。从分子识别的角度来看，葡聚糖是对配体的挑战，因为它们彼此之间的不同仅仅是因为它们之间的连接点不同，或者是单个羟基的位置不同。此外，基于葡聚糖的生物聚合物是灵活的和高度水合的。该项目的目标是在分子水平上了解模型系统中蛋白质-葡聚糖的相互作用，并利用这一知识通过集成的计算和实验策略开发新的糖链识别蛋白质。从一种天然的葡聚糖结合蛋白-氰化韦林开始，我们将在实验侧利用定向进化，在计算侧利用快速对接方法以及显式溶剂分子动力学模拟，探索支持高亲和力结合到靶糖链的序列空间。这一提议的更广泛的影响是双重的。首先，该项目依赖于高度跨学科的方法，为研究生和本科生提供丰富的培训经验。第二，在爱荷华州和亚利桑那州立大学，私人助理都参加高中一级的外展活动。在亚利桑那州立大学，厄兹坎和吉兰达参与了由CRESMET(http://cresmet.asu.edu/MSTF/index.shtml).)运营的亚利桑那大学数学和科学教学研究员计划的这个项目该项目将凤凰城地区贫困学校的高中教师带到亚利桑那州立大学进行研究实习，并结合科学教育技术的强化培训，并通过校园访问在学校和大学之间建立了融洽的关系。马古利斯创建了一个导师配对计划(http://mentor.chem.uiowa.edu/))，通过向上绑定计划将未被充分代表的高中生纳入研究小组。