COMPLEX FORMATION AND BINDING AFFINITY OF NHERF1 TO C-TERMINAL PEPTIDES

NHERF1 与 C 端肽的复合物形成和结合亲和力

• 批准号: 8364344
• 负责人: Peter A Friedman
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364344
• 关键词: Affinity; Amino Acids; Binding; Biological; Biomedical Research; C-terminal; Complex; Funding; Grant; High Performance Computing; Ligands; Modeling; Molecular Models; National Center for Research Resources; Peptides; Post-Translational Protein Processing; Principal Investigator; Research; Research Infrastructure; Resources; Source; United States National Institutes of Health; cost; molecular dynamics; molecular modeling; receptor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Using Molecular Dynamic (MD) simulations and computational protein modification, we will characterize PDZ-ligand complexes of the Na/H Exchange Regulatory Factor-1 (NHERF1) due to their biological and medicinal importance. We will investigate the PDZ1/PDZ2-ligand interactions. To probe such interactions we will use the five amino acid residue carboxy-terminal recognition motifs from the NaPi cotransporter (NATRL; L1), PTH receptor (WETVM; L2) or NHERF1(LFSNL; L3). We will estimate the binding affinity of PDZ1 for both L1 and L2 and PDZ2 for L2 and L3. By combining molecular modeling of isolated PDZ domains, a model for tandem PDZ1-PDZ2 will be proposed.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 使用分子动力学 (MD) 模拟和计算蛋白质修饰，我们将表征 Na/H 交换调节因子 1 (NHERF1) 的 PDZ-配体复合物，因为它们具有生物学和医学重要性。我们将研究 PDZ1/PDZ2 配体相互作用。为了探究这种相互作用，我们将使用来自 NaPi 协同转运蛋白（NATRL；L1）、PTH 受体（WETVM；L2）或 NHERF1（LFSNL；L3）的五个氨基酸残基羧基末端识别基序。我们将估计 PDZ1 对 L1 和 L2 的结合亲和力以及 PDZ2 对 L2 和 L3 的结合亲和力。通过结合孤立的 PDZ 结构域的分子建模，将提出串联 PDZ1-PDZ2 的模型。