Plasticity in the Recognition of Flexible Ligands

柔性配体识别中的可塑性

• 批准号: 1121842
• 负责人: Deborah Wuttke
• 金额: $ 96.2万
• 依托单位: University of Colorado at Boulder
• 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 2017-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1121842&HistoricalAwards=false
• 关键词: Plasticity; Recognition; Flexible; Ligands

This research project aims to understand the role of structural plasticity in mediating binding specificity and affinity between protein domains and flexible ligands. The specific recognition of a ligand is the key function of many proteins, and forms the basis of the extensive networks that coordinate the activities of central biological processes. In many biological contexts, a protein domain functionally recognizes a family of related ligands while discriminating against structurally similar ligands. The hypothesis to be tested is that the recognition of related ligands is more structurally diverse than can be inferred from a single structure of a protein-ligand complex. The rigorous biochemical and structural analysis of the ensemble of conformations adopted at biomolecular interfaces that is part of this research program will contribute to our understanding of the underlying mechanisms of ligand-binding specificity. Furthermore, this knowledge will provide insights for computational efforts aimed at understanding and predicting ligand-binding specificity. This work will significantly advance our understanding of the mechanisms that confer specificity in protein-ligand interactions, which are essential to a wide variety of biological functions. In addition, the structural and biochemical data will complement ongoing computational studies by others that seek to model protein-ligand interactions. Furthermore, the program outlined here promotes teaching, training and learning while advancing scientific discovery. These activities occur through a well-designed and thoughtful postdoctoral fellow and graduate student mentoring program, as well as through teaching innovations in the undergraduate classroom. The PI also participates in several programs to increase the participation of under-represented groups, including women and minorities in science, ranging from faculty, postdoctoral fellow and graduate student career mentoring to tailoring the graduate curriculum to facilitate recruitment and retention of under-represented minorities. This program supports the use of our regional high field NMR facilities, including 800 and 900 MHz instruments equipped with cryogenic probes. In addition to the normal avenues of dissemination of research findings, including peer-reviewed publication and presentations at scientific meetings, the PI participates in community outreach through science activities at local schools and as a CU Wizard, orchestrating a community science show.

本研究项目旨在了解结构可塑性在调节蛋白结构域与柔性配体结合特异性和亲和力中的作用。对配体的特异性识别是许多蛋白质的关键功能，并形成协调中心生物过程活动的广泛网络的基础。在许多生物学背景下，蛋白质结构域在功能上识别一个相关配体家族，同时对结构相似的配体进行歧视。要验证的假设是，对相关配体的识别在结构上比从蛋白质-配体复合物的单一结构推断出来的更多样化。作为本研究项目的一部分，对生物分子界面上的构象集合进行严格的生化和结构分析，将有助于我们理解配体结合特异性的潜在机制。此外，这些知识将为旨在理解和预测配体结合特异性的计算工作提供见解。这项工作将极大地促进我们对蛋白质-配体相互作用特异性机制的理解，这对多种生物功能至关重要。此外，结构和生化数据将补充其他人正在进行的计算研究，以寻求蛋白质-配体相互作用的模型。此外，这里概述的计划在推进科学发现的同时促进了教学、培训和学习。这些活动通过精心设计和周到的博士后和研究生指导计划以及在本科课堂上的教学创新来实现。该计划还参与了几个项目，以增加包括妇女和少数民族在内的代表性不足群体在科学领域的参与，从教师、博士后和研究生的职业指导到定制研究生课程，以促进代表性不足的少数民族的招聘和保留。该计划支持使用我们的区域高场核磁共振设施，包括配备低温探针的800和900 MHz仪器。除了常规的传播研究成果的途径，包括同行评审的出版物和在科学会议上的报告，PI通过在当地学校的科学活动参与社区外展，并作为CU向导，策划社区科学展览。

项目成果

Diversity in peptide recognition by the SH2 domain of SH2B1

• DOI: 10.1002/prot.25420
• 发表时间: 2018-02-01
• 期刊: PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
• 影响因子: 2.9
• 作者: McKercher, Marissa A.;Guan, Xiaoyang;Wuttke, Deborah S.
• 通讯作者: Wuttke, Deborah S.